327 results match your criteria Alzheimer Disease in Individuals With Down Syndrome


Frontal-subcortical behaviors during Alzheimer's disease in individuals with Down syndrome.

Neurobiol Aging 2019 Mar 11;78:186-194. Epub 2019 Mar 11.

Obsessive-Compulsive Spectrum Disorders Program, PROTOC, Department and Institute of Psychiatry, University of São Paulo School of Medicine, FMUSP, São Paulo, Brazil.

There is evidence that frontal-subcortical circuits play an important role in the initial presentation of dementia in Down syndrome (DS), including changes in behavior, a decline in working memory and executive dysfunction. We evaluated 92 individuals with DS (≥30 years of age), divided into 3 groups by diagnosis-stable cognition, prodromal dementia, and Alzheimer's disease. Each individual was evaluated with an executive protocol developed for people with intellectual disabilities and was rated for behaviors related to frontal lobe dysfunction (disinhibition, executive dysfunction, and apathy) by an informant using the Frontal Systems Behavior Scale. Read More

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http://dx.doi.org/10.1016/j.neurobiolaging.2019.02.028DOI Listing
March 2019
4 Reads

The effect of acute exercise on the performance of verbal fluency in adolescents and young adults with Down syndrome: a pilot study.

J Intellect Disabil Res 2019 Feb 27. Epub 2019 Feb 27.

School of Health Solutions, Arizona State University, Phoenix, AZ, USA.

Background: The high prevalence of cognitive dysfunction is well documented in individuals with Down syndrome. However, only a few studies have focused on the effect of exercise on cognitive performance in this population. In particular, verbal fluency has been shown to be relevant to the early onset of Alzheimer's disease in individuals with Down syndrome. Read More

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http://dx.doi.org/10.1111/jir.12603DOI Listing
February 2019
1 Read

Dementia in Down syndrome: unique insights for Alzheimer disease research.

Nat Rev Neurol 2019 Mar;15(3):135-147

Sanders Brown Center on Aging, University of Kentucky, Lexington, KY, USA.

Virtually all adults with Down syndrome (DS) show the neuropathological changes of Alzheimer disease (AD) by the age of 40 years. This association is partially due to overexpression of amyloid precursor protein, encoded by APP, as a result of the location of this gene on chromosome 21. Amyloid-β accumulates in the brain across the lifespan of people with DS, which provides a unique opportunity to understand the temporal progression of AD and the epigenetic factors that contribute to the age of dementia onset. Read More

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http://dx.doi.org/10.1038/s41582-018-0132-6DOI Listing
March 2019
6 Reads

Alzheimer's disease in Down syndrome: An overlooked population for prevention trials.

Alzheimers Dement (N Y) 2018 13;4:703-713. Epub 2018 Dec 13.

Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.

The discovery that adults with Down syndrome (DS) have neuropathological features identical to individuals with sporadic Alzheimer's disease (AD) played a key role in the identification of the amyloid precursor protein gene on chromosome 21 and resulted in the amyloid cascade hypothesis. Individuals with DS have a lifetime risk for dementia in excess of 90%, and DS is now acknowledged to be a genetic form of AD similar to rare autosomal-dominant causes. Just as DS put the spotlight on amyloid precursor protein mutations, it is also likely to inform us of the impact of manipulating the amyloid pathway on treatment outcomes in AD. Read More

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http://dx.doi.org/10.1016/j.trci.2018.10.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6296162PMC
December 2018
13 Reads

Cognitive markers of preclinical and prodromal Alzheimer's disease in Down syndrome.

Alzheimers Dement 2019 Feb 28;15(2):245-257. Epub 2018 Nov 28.

Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; Division of Psychiatry, University College London, London, UK; The LonDownS Consortium, London, UK.

Introduction: Down syndrome (DS) is associated with an almost universal development of Alzheimer's disease. Individuals with DS are therefore an important population for randomized controlled trials to prevent or delay cognitive decline, though it is essential to understand the time course of early cognitive changes.

Methods: We conducted the largest cognitive study to date with 312 adults with DS to assess age-related and Alzheimer's disease-related cognitive changes during progression from preclinical to prodromal dementia, and prodromal to clinical dementia. Read More

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http://dx.doi.org/10.1016/j.jalz.2018.08.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6374283PMC
February 2019
5 Reads

Association of Dementia With Mortality Among Adults With Down Syndrome Older Than 35 Years.

JAMA Neurol 2018 Nov 19. Epub 2018 Nov 19.

Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, England.

Importance: This work quantifies the fatal burden of dementia associated with Alzheimer disease in individuals with Down syndrome (DS).

Objective: To explore the association of dementia associated with Alzheimer disease with mortality and examine factors associated with dementia in adults with DS.

Design, Settings And Participants: Prospective longitudinal study in a community setting in England. Read More

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http://dx.doi.org/10.1001/jamaneurol.2018.3616DOI Listing
November 2018
16 Reads

Prevalence and Severity of Alzheimer Disease in Individuals With Down Syndrome.

JAMA Neurol 2018 Nov 19. Epub 2018 Nov 19.

Down Syndrome Program, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.

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http://dx.doi.org/10.1001/jamaneurol.2018.3443DOI Listing
November 2018
2 Reads

Intranasal rapamycin ameliorates Alzheimer-like cognitive decline in a mouse model of Down syndrome.

Transl Neurodegener 2018 6;7:28. Epub 2018 Nov 6.

1Department of Biochemical Sciences, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy.

Background: Down syndrome (DS) individuals, by the age of 40s, are at increased risk to develop Alzheimer-like dementia, with deposition in brain of senile plaques and neurofibrillary tangles. Our laboratory recently demonstrated the disturbance of PI3K/AKT/mTOR axis in DS brain, prior and after the development of Alzheimer Disease (AD). The aberrant modulation of the mTOR signalling in DS and AD age-related cognitive decline affects crucial neuronal pathways, including insulin signaling and autophagy, involved in pathology onset and progression. Read More

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https://translationalneurodegeneration.biomedcentral.com/art
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http://dx.doi.org/10.1186/s40035-018-0133-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6218962PMC
November 2018
17 Reads

Restoring microglial and astroglial homeostasis using DNA immunization in a Down Syndrome mouse model.

Brain Behav Immun 2019 Jan 25;75:163-180. Epub 2018 Oct 25.

The Leslie and Susan Gonda Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat Gan 5290002, Israel; The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 5290002, Israel; The Paul Feder Laboratory on Alzheimer's Disease Research, Bar-Ilan University, Ramat Gan 5290002, Israel. Electronic address:

Down Syndrome (DS), the most common cause of genetic intellectual disability, is characterized by over-expression of the APP and DYRK1A genes, located on the triplicated chromosome 21. This chromosomal abnormality leads to a cognitive decline mediated by Amyloid-β (Aβ) overproduction and tau hyper-phosphorylation as early as the age of 40. In this study, we used the Ts65Dn mouse model of DS to evaluate the beneficial effect of a DNA vaccination against the Aβ fragment, in ameliorating Aβ-related neuropathology and rescue of cognitive and behavioral abilities. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S08891591183074
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http://dx.doi.org/10.1016/j.bbi.2018.10.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358279PMC
January 2019
13 Reads

Comparison of longitudinal Aβ in nondemented elderly and Down syndrome.

Neurobiol Aging 2019 Jan 27;73:171-176. Epub 2018 Sep 27.

Department of Psychiatry, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA. Electronic address:

Down syndrome (DS) predisposes individuals to early Alzheimer's disease (AD). Using Pittsburgh Compound B ([C]PiB), a pattern of striatal amyloid beta (Aβ) that is elevated relative to neocortical binding has been reported, similar to that of nondemented autosomal dominant AD mutation carriers. However, it is not known whether changes in striatal and neocortical [C]PiB retention differ over time in a nondemented DS population when compared to changes in a nondemented elderly (NDE) population. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S01974580183035
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http://dx.doi.org/10.1016/j.neurobiolaging.2018.09.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251757PMC
January 2019
7 Reads

[The behavioral and psychological symptoms of dementia in down syndrome (BPSD-DS) scale: comprehensive assessment of psychopathology in down syndrome].

Tijdschr Gerontol Geriatr 2018 Oct 20;49(5):187-205. Epub 2018 Sep 20.

Afdeling Neurologie en Alzheimer Onderzoekscentrum, Universitair Medisch Centrum Groningen, Rijksuniversiteit Groningen, postbus 30.001, 9700 RB, Groningen, Nederland.

Behavioral and psychological symptoms of dementia (BPSD) have not been comprehensively studied in people with Down syndrome, despite their high risk on dementia. A novel evaluation scale was developed to identify the nature, frequency and severity of behavioral changes (83 behavioral items in 12 clinically defined sections). Central aim was to identify items that change in relation to the dementia status. Read More

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http://dx.doi.org/10.1007/s12439-018-0262-8DOI Listing
October 2018
11 Reads

Elimination of amyloid precursor protein in senile plaques in the brain of a patient with Alzheimer-type dementia and Down syndrome.

Brain Dev 2019 Jan 4;41(1):106-110. Epub 2018 Aug 4.

Department of Child Neurology, Tokyo Metropolitan Tobu Medical Center for Persons with Developmental/Multiple Disabilities, Japan.

The average lifespan of individuals with Down syndrome has approximately doubled over the past three decades to 55-60 years. To reveal the pathogenic process of Alzheimer-type dementia in individuals with Down syndrome, we immunohistochemically examined senile plaque formation in the cerebral cortex in the autopsy brain and compared findings with our previous studies. We described a 52-year-old female with Down syndrome who developed progressively more frequent myoclonus following cognitive decline and died at the age of 59 years. Read More

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http://dx.doi.org/10.1016/j.braindev.2018.07.017DOI Listing
January 2019
6 Reads

Prevalence of Aging, Dementia, and Multimorbidity in Older Adults With Down Syndrome.

JAMA Neurol 2018 Nov;75(11):1399-1406

Global Brain Health Institute, University of California, San Francisco.

Importance: As the life expectancy of people with Down syndrome (DS) has markedly increased over the past decades, older adults with DS may be experiencing a higher incidence of aging conditions. In addition to longevity, the amyloid precursor protein gene located on chromosome 21 places individuals with DS at a high risk for developing Alzheimer disease. Yet, few studies have determined prevalence of dementia and comorbidities among older people with DS. Read More

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http://archneur.jamanetwork.com/article.aspx?doi=10.1001/jam
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http://dx.doi.org/10.1001/jamaneurol.2018.2210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6248113PMC
November 2018
25 Reads

Signs indicating dementia in Down, Williams and Fragile X syndromes.

Mol Genet Genomic Med 2018 09 3;6(5):855-860. Epub 2018 Jul 3.

KTO-Special Welfare District of Varsinais-Suomi, Paimio, Finland.

Background: Intellectual disability (ID) and dementia reflect disturbed cortical function during and after developmental age, respectively. Due to the wide heterogeneity of ID population the decline in cognitive and adaptive skills may be different in distinct genetic subgroups.

Methods: Using the British Present Psychiatric State-learning Disabilities assessment (PPS-LD) questionnaire the dementia signs were screened in 62, 22 and 44 individuals (> 35 year of age) with Down (DS, OMIM number 190685), Williams (WS, OMIM number, 194050), and Fragile X syndrome (FXS, OMIM number 309550), respectively. Read More

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http://dx.doi.org/10.1002/mgg3.430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6160716PMC
September 2018
3 Reads

A longitudinal study of brain anatomy changes preceding dementia in Down syndrome.

Neuroimage Clin 2018 28;18:160-166. Epub 2018 Jan 28.

Specialized Service in Mental Health and Intellectual Disability, Institut Assistència Sanitària (IAS), Parc Hospitalari Martí i Julià, 17190 Girona, Spain.

Background: We longitudinally assessed Down syndrome individuals at the age of risk of developing dementia to measure changes in brain anatomy and their relationship to cognitive impairment progression.

Methods: Forty-two Down syndrome individuals were initially included, of whom 27 (mean age 46.8 years) were evaluable on the basis of completing the 2-year follow-up and success in obtaining good quality MRI exams. Read More

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http://dx.doi.org/10.1016/j.nicl.2018.01.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5984600PMC
January 2019
6 Reads

Monoaminergic impairment in Down syndrome with Alzheimer's disease compared to early-onset Alzheimer's disease.

Alzheimers Dement (Amst) 2018 23;10:99-111. Epub 2017 Nov 23.

Department of Neurology and Alzheimer Research Center, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Introduction: People with Down syndrome (DS) are at high risk for Alzheimer's disease (AD). Defects in monoamine neurotransmitter systems are implicated in DS and AD but have not been comprehensively studied in DS.

Methods: Noradrenaline, adrenaline, and their metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG); dopamine and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid; and serotonin and its metabolite 5-hydroxyindoleacetic acid were quantified in 15 brain regions of DS without AD (DS, n = 4), DS with AD (DS+AD, n = 17), early-onset AD (EOAD, n = 11) patients, and healthy non-DS controls (n = 10) in the general population. Read More

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http://dx.doi.org/10.1016/j.dadm.2017.11.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5956808PMC
November 2017
15 Reads

The Behavioral and Psychological Symptoms of Dementia in Down Syndrome (BPSD-DS) Scale: Comprehensive Assessment of Psychopathology in Down Syndrome.

J Alzheimers Dis 2018 ;63(2):797-819

Department of Neurology and Alzheimer Research Center, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

People with Down syndrome (DS) are prone to develop Alzheimer's disease (AD). Behavioral and psychological symptoms of dementia (BPSD) are core features, but have not been comprehensively evaluated in DS. In a European multidisciplinary study, the novel Behavioral and Psychological Symptoms of Dementia in Down Syndrome (BPSD-DS) scale was developed to identify frequency and severity of behavioral changes taking account of life-long characteristic behavior. Read More

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http://www.medra.org/servlet/aliasResolver?alias=iospress&am
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http://dx.doi.org/10.3233/JAD-170920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5929348PMC
January 2018
12 Reads

Analysis of the linguistic profile in down syndrome using the arizona battery for communication disorders of dementia - a pilot study.

Codas 2018 Mar 12;30(2):e20170164. Epub 2018 Mar 12.

Departamento de Psiquiatria, Faculdade de Medicina da Universidade de São Paulo - USP - São Paulo (SP), Brazil.

Purpose: To characterize the linguistic profile of adults and elderly with Down Syndrome (DS) using the Arizona Battery for Communication Disorders of Dementia (ABCD).

Methods: Thirty adult individuals with DS were evaluated through the MoCA cognitive battery, four functional scales (Pfeffer, Lawton-IADL, Katz-IADL and IQCODE) and the ABCD battery, which evaluates Mental State, Episodic Memory, Linguistic Expression, Linguistic Comprehension and Visuospatial Construction. The scores obtained by the individuals in the ABCD were correlated to those obtained on the Lawton-IADL scale. Read More

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http://dx.doi.org/10.1590/2317-1782/20182017164DOI Listing
March 2018
15 Reads

Atypical Localization and Dissociation between Glucose Uptake and Amyloid Deposition in Cognitively Normal APOE*E4 Homozygotic Elders Compared with Patients with Late-Onset Alzheimer's Disease.

eNeuro 2018 Jan-Feb;5(1). Epub 2018 Feb 28.

Cognitive Neuroimaging Unit, Mental Health Service Line, Minneapolis Veterans Health Care System, Minneapolis, MN 55417.

Alzheimer's disease (AD) progresses insidiously over decades. Therefore, study of preclinical AD is critical to identify early pathophysiological changes as potential targets for prevention or treatment. The brain processes at the preclinical stage remain minimally understood. Read More

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http://dx.doi.org/10.1523/ENEURO.0396-17.2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5830350PMC
January 2019
6 Reads

Erythromyeloid-Derived TREM2: A Major Determinant of Alzheimer's Disease Pathology in Down Syndrome.

J Alzheimers Dis 2018 ;61(3):1143-1162

Department of Psychiatry, Cambridge Intellectual and Developmental Disabilities Research Group, University of Cambridge, Cambridge, UK.

Background: Down syndrome (DS; trisomy 21) individuals have a spectrum of hematopoietic and neuronal dysfunctions and by the time they reach the age of 40 years, almost all develop Alzheimer's disease (AD) neuropathology which includes senile plaques and neurofibrillary tangles. Inflammation and innate immunity are key players in AD and DS. Triggering receptor expressed in myeloid cells-2 (TREM2) variants have been identified as risk factors for AD and other neurodegenerative diseases. Read More

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http://dx.doi.org/10.3233/JAD-170814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5817909PMC
January 2019
10 Reads

Cerebrovascular pathology in Down syndrome and Alzheimer disease.

Acta Neuropathol Commun 2017 Dec 1;5(1):93. Epub 2017 Dec 1.

Department of Pediatrics, University of California, Irvine, Irvine, CA, USA.

People with Down syndrome (DS) are at high risk for developing Alzheimer disease (AD) with age. Typically, by age 40 years, most people with DS have sufficient neuropathology for an AD diagnosis. Interestingly, atherosclerosis and hypertension are atypical in DS with age, suggesting the lack of these vascular risk factors may be associated with reduced cerebrovascular pathology. Read More

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http://dx.doi.org/10.1186/s40478-017-0499-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5709935PMC
December 2017
10 Reads

The neuronal and endocrine roles of RCAN1 in health and disease.

Clin Exp Pharmacol Physiol 2018 04 29;45(4):377-383. Epub 2017 Nov 29.

College of Medicine and Public Health and Centre for Neuroscience, Flinders University, Adelaide, SA, Australia.

The regulator of calcineurin 1 (RCAN1) was first discovered as a gene located on human chromosome 21, expressed in neurons and overexpressed in the brains of Down syndrome individuals. Increased expression of RCAN1 has been linked with not only Down syndrome-associated pathology but also an associated neurological disorder, Alzheimer's Disease, in which neuronal RCAN1 expression is also increased. RCAN1 has additionally been demonstrated to affect other cell types including endocrine cells, with links to the pathogenesis of β-cell dysfunction in type 2 diabetes. Read More

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http://dx.doi.org/10.1111/1440-1681.12884DOI Listing
April 2018
8 Reads

Dysfunction of autophagy and endosomal-lysosomal pathways: Roles in pathogenesis of Down syndrome and Alzheimer's Disease.

Free Radic Biol Med 2018 01 6;114:40-51. Epub 2017 Oct 6.

Center for Dementia Research, Nathan S. Kline Institute, Orangeburg, NY 10962, USA; Department of Psychiatry, New York University Langone Medical Center, New York, NY 10016, USA; Department of Cell Biology, New York University Langone Medical Center, New York, NY 10016, USA. Electronic address:

Individuals with Down syndrome (DS) have an increased risk of early-onset Alzheimer's Disease (AD), largely owing to a triplication of the APP gene, located on chromosome 21. In DS and AD, defects in endocytosis and lysosomal function appear at the earliest stages of disease development and progress to widespread failure of intraneuronal waste clearance, neuritic dystrophy and neuronal cell death. The same genetic factors that cause or increase AD risk are also direct causes of endosomal-lysosomal dysfunction, underscoring the essential partnership between this dysfunction and APP metabolites in AD pathogenesis. Read More

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http://dx.doi.org/10.1016/j.freeradbiomed.2017.10.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5748263PMC
January 2018
24 Reads

Searching for new pharmacological targets for the treatment of Alzheimer's disease in Down syndrome.

Eur J Pharmacol 2017 Dec 5;817:7-19. Epub 2017 Oct 5.

Department of Neurology and Neurosurgery, McGill University, Montreal, Canada H3G1Y6; Department of Anatomy and Cell Biology, McGill University, Montreal, Canada H3G1Y6; Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada H3G1Y6. Electronic address:

Individuals with Down syndrome are at increased risk of developing Alzheimer's disease due to increase gene dosage resulting from chromosome 21 triplication. Although virtually all adults with Down syndrome will exhibit the major neuropathological hallmarks that define Alzheimer's disease, not all of them will develop the clinical symptoms associated with this disorder (i.e. Read More

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http://dx.doi.org/10.1016/j.ejphar.2017.10.004DOI Listing
December 2017
39 Reads

Clinical aspects and biomarkers of Alzheimer's disease in Down syndrome.

Free Radic Biol Med 2018 01 1;114:3-9. Epub 2017 Sep 1.

Division of Psychiatry, University College London, London, UK; Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neurosciences, King's College London, London, UK; The LonDownS Consortium, London, UK. Electronic address:

Alzheimer's disease (AD) may affect in excess of 90% of individuals with Down syndrome (DS) after age 60, due to duplication of the APP gene in trisomy of chromosome 21, with neuropathology that is comparable to Sporadic AD and Familial AD (FAD). Previous literature suggested some unique features in clinical presentation of dementia in DS (DSd), which might be due to diagnostic difficulties, or represent a real difference compared to SAD or FAD. We review current knowledge on clinical diagnosis and presentation of dementia in DS in comparison with FAD due to APP mutations and APP duplication. Read More

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http://dx.doi.org/10.1016/j.freeradbiomed.2017.08.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6451620PMC
January 2018
61 Reads

Quantification of plasma phosphorylated tau to use as a biomarker for brain Alzheimer pathology: pilot case-control studies including patients with Alzheimer's disease and down syndrome.

Mol Neurodegener 2017 09 4;12(1):63. Epub 2017 Sep 4.

Department of Neurology, Kyoto Prefectural University of Medicine, Kyoto, 602-0841, Japan.

Background: There is still a substantial unmet need for less invasive and lower-cost blood-based biomarkers to detect brain Alzheimer's disease (AD) pathology. This study is aimed to determine whether quantification of plasma tau phosphorylated at threonine 181 (p-tau181) is informative in the diagnosis of AD.

Methods: We have developed a novel ultrasensitive immunoassay to quantify plasma p-tau181, and measured the levels of plasma p-tau181 in three cohorts. Read More

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http://dx.doi.org/10.1186/s13024-017-0206-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5582385PMC
September 2017
93 Reads

Longitudinal telomere shortening and early Alzheimer's disease progression in adults with down syndrome.

Am J Med Genet B Neuropsychiatr Genet 2017 Dec 30;174(8):772-778. Epub 2017 Aug 30.

The Kennedy Krieger Institute and Johns Hopkins University School of Medicine, Baltimore, Maryland.

Telomere shortening was shown to parallel Alzheimer's disease (AD) associated dementia. By using a dual PNA Probe system we have developed a practical method for comparing telomere length in T-lymphocyte interphases from individuals with Down syndrome (DS) with and without "mild cognitive impairment" (MCI-DS) and demonstrated that telomere length can serve as a valid biomarker for the onset of MCI-DS in this high-risk population. To verify progressive cognitive decline we have now examined sequential changes in telomere length in 10 adults with DS (N = 4 Female, N = 6 Male) developing MCI-DS. Read More

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http://dx.doi.org/10.1002/ajmg.b.32575DOI Listing
December 2017
19 Reads

Early increased density of cyclooxygenase-2 (COX-2) immunoreactive neurons in Down syndrome.

Folia Neuropathol 2017 ;55(2):154-160

Neuroinflammation is one of the hallmarks of Alzheimer's disease. One of the enzymes involved in neuroinflammation, even in early stages of the disease, is COX-2, an inducible cyclooxygenase responsible for the generation of eicosanoids and for the generation of free radicals. Individuals with Down syndrome develop Alzheimer's disease early in life. Read More

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http://dx.doi.org/10.5114/fn.2017.68582DOI Listing
February 2018
6 Reads

The physiological role of the amyloid precursor protein as an adhesion molecule in the developing nervous system.

J Neurochem 2017 10 15;143(1):11-29. Epub 2017 Aug 15.

Laboratorio de Neuropatología Experimental, Instituto de Investigación Médica Mercedes y Martín Ferreyra, INIMEC-CONICET-Universidad Nacional de Córdoba, Córdoba, Argentina.

The amyloid precursor protein (APP) is a type I transmembrane glycoprotein better known for its participation in the physiopathology of Alzheimer disease as the source of the beta amyloid fragment. However, the physiological functions of the full length protein and its proteolytic fragments have remained elusive. APP was first described as a cell-surface receptor; nevertheless, increasing evidence highlighted APP as a cell adhesion molecule. Read More

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http://dx.doi.org/10.1111/jnc.14122DOI Listing
October 2017
25 Reads

Normalizing the gene dosage of Dyrk1A in a mouse model of Down syndrome rescues several Alzheimer's disease phenotypes.

Neurobiol Dis 2017 Oct 21;106:76-88. Epub 2017 Jun 21.

Department of Physiology and Pharmacology, Faculty of Medicine, University of Cantabria, Santander, Spain. Electronic address:

The intellectual disability that characterizes Down syndrome (DS) is primarily caused by prenatal changes in central nervous system growth and differentiation. However, in later life stages, the cognitive abilities of DS individuals progressively decline due to accelerated aging and the development of Alzheimer's disease (AD) neuropathology. The AD neuropathology in DS has been related to the overexpression of several genes encoded by Hsa21 including DYRK1A (dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A), which encodes a protein kinase that performs crucial functions in the regulation of multiple signaling pathways that contribute to normal brain development and adult brain physiology. Read More

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http://dx.doi.org/10.1016/j.nbd.2017.06.010DOI Listing
October 2017
10 Reads

Longitudinal changes in amyloid positron emission tomography and volumetric magnetic resonance imaging in the nondemented Down syndrome population.

Alzheimers Dement (Amst) 2017 23;9:1-9. Epub 2017 May 23.

University of Wisconsin-Madison, Madison, WI, USA.

Introduction: Down syndrome (DS) arises from a triplication of chromosome 21, causing overproduction of the amyloid precursor protein and predisposes individuals to early Alzheimer's disease (AD).

Methods: Fifty-two nondemented adults with DS underwent two cycles of carbon 11-labeled Pittsburgh compound B ([C]PiB) and T1 weighted magnetic resonance imaging (MRI) scans 3.0 ± 0. Read More

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http://dx.doi.org/10.1016/j.dadm.2017.05.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454131PMC
May 2017
54 Reads

C-terminal fragments of the amyloid precursor protein in cerebrospinal fluid as potential biomarkers for Alzheimer disease.

Sci Rep 2017 05 30;7(1):2477. Epub 2017 May 30.

Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, 03550, Sant Joan d'Alacant, Alicante, España.

This study assesses whether C-terminal fragments (CTF) of the amyloid precursor protein (APP) are present in cerebrospinal fluid (CSF) and their potential as biomarkers for Alzheimer's disease (AD). Immunoprecipitation and simultaneous assay by Western blotting using multiplex fluorescence imaging with specific antibodies against particular domains served to characterize CTFs of APP in human CSF. We demonstrate that APP-CTFs are detectable in human CSF, being the most abundant a 25-kDa fragment, probably resulting from proteolytic processing by η-secretase. Read More

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http://dx.doi.org/10.1038/s41598-017-02841-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5449401PMC
May 2017
23 Reads

Candidate gene analysis for Alzheimer's disease in adults with Down syndrome.

Neurobiol Aging 2017 08 3;56:150-158. Epub 2017 May 3.

Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Taub Institute, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Epidemiology, School of Public Health, Columbia University, New York, NY, USA.

Individuals with Down syndrome (DS) overexpress many genes on chromosome 21 due to trisomy and have high risk of dementia due to the Alzheimer's disease (AD) neuropathology. However, there is a wide range of phenotypic differences (e.g. Read More

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http://dx.doi.org/10.1016/j.neurobiolaging.2017.04.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5603247PMC
August 2017
45 Reads

Cerebral amyloid angiopathy in Down syndrome and sporadic and autosomal-dominant Alzheimer's disease.

Alzheimers Dement 2017 Nov 29;13(11):1251-1260. Epub 2017 Apr 29.

Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Barcelona Down Medical Center, Fundació Catalana de Síndrome de Down, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED, Madrid, Spain. Electronic address:

Introduction: We aimed to investigate if cerebral amyloid angiopathy (CAA) is more frequent in genetically determined than in sporadic early-onset forms of Alzheimer's disease (AD) (early-onset AD [EOAD]).

Methods: Neuroimaging features of CAA, apolipoprotein (APOE), and cerebrospinal fluid amyloid β (Aβ) 40 levels were studied in subjects with Down syndrome (DS, n = 117), autosomal-dominant AD (ADAD, n = 29), sporadic EOAD (n = 42), and healthy controls (n = 68).

Results: CAA was present in 31%, 38%, and 12% of cognitively impaired DS, symptomatic ADAD, and sporadic EOAD subjects and in 13% and 4% of cognitively unimpaired DS individuals and healthy controls, respectively. Read More

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http://dx.doi.org/10.1016/j.jalz.2017.03.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5660938PMC
November 2017
23 Reads

The physiological phosphorylation of tau is critically changed in fetal brains of individuals with Down syndrome.

Neuropathol Appl Neurobiol 2018 04 25;44(3):314-327. Epub 2017 May 25.

Institute of Neurology, Neurodegeneration Research Group, Medical University of Vienna, Vienna, Austria.

Aims: Down syndrome (DS) is a common cause of mental retardation accompanied by cognitive impairment. Comprehensive studies suggested a link between development and ageing, as nearly all individuals with DS develop Alzheimer disease (AD)-like pathology. However, there is still a paucity of data on tau in early DS to support this notion. Read More

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http://doi.wiley.com/10.1111/nan.12406
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http://dx.doi.org/10.1111/nan.12406DOI Listing
April 2018
7 Reads

Cerebrospinal fluid biomarkers for Alzheimer's disease in Down syndrome.

Alzheimers Dement (Amst) 2017 20;8:1-10. Epub 2017 Mar 20.

Department of Neurology and Alzheimer Research Center, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Down syndrome (DS), present in nearly six million people, is associated with an extremely high risk to develop Alzheimer's disease (AD). Amyloid-β and tau pathology are omnipresent from age 40 years onward, but clinical symptoms do not appear in all DS individuals. Dementia diagnostics is complex in this population, illustrating the great need for predictive biomarkers. Read More

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http://dx.doi.org/10.1016/j.dadm.2017.02.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5384293PMC
March 2017
10 Reads

Early detection of dementia in people with an intellectual disability - A German pilot study.

J Appl Res Intellect Disabil 2017 Dec 23;30 Suppl 1:49-57. Epub 2017 Mar 23.

Faculty of Social Work, Ostfalia University of Applied Sciences, Wolfenbüttel, Germany.

Background: This study investigated the application of a newly developed neuropsychological assessment, the Wolfenbütteler Dementia Test for Individuals with Intellectual Disabilities (WDTIM) in combination with the Dementia Screening Questionnaire for Individuals with Intellectual Disabilities (DSQIID).

Methods: The instruments were evaluated in a prospective 2-year follow-up study. A total of 102 people with an intellectual disability were assessed at 6-month intervals. Read More

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http://dx.doi.org/10.1111/jar.12347DOI Listing
December 2017
19 Reads

A Multicentre Italian Validation Study in Aging Adults with Down Syndrome and Other Forms of Intellectual Disabilities: Dementia Screening Questionnaire for Individuals with Intellectual Disabilities.

Curr Alzheimer Res 2017 ;14(7):709-721

Dementia Program, Local Health District, Modena. Italy.

Background: The USA National Task Group (NTG) guidelines advocate the use of an adapted version of Dementia Screening Questionnaire for Individuals with Intellectual Disabilities (DSQIID) for dementia screening of individuals with Down syndrome (DS) and with other forms of ID (non-DS).

Objective: In order to meet these guidelines, this study verifies the psychometric properties of an Italian version of the original DSQIID in a population composed of adults aged 40 years and over with DS and non-DS ID.

Methods: Internal consistency, inter-rater and intra-rater reliabilities, structural validity, convergent validity and known group differences of DSQIID-I were assessed with 200 individuals with ID (mean of 55. Read More

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http://dx.doi.org/10.2174/1567205014666170117094757DOI Listing
April 2018
37 Reads

Cognitive decline and dementia in Down syndrome.

Curr Opin Psychiatry 2017 Mar;30(2):102-107

Division of Psychiatry, University College London, London, United Kingdom.

Purpose Of Review: Alzheimer's disease is most likely universal in older individuals with Down syndrome, due to having three copies of the amyloid precursor protein gene, resulting in amyloid-beta plaque deposition. Down syndrome is an important population in which to consider clinical trials of treatments to prevent or delay the development of dementia. However, assessment of subtler cognitive changes is challenging due to the presence of intellectual disability. Read More

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http://dx.doi.org/10.1097/YCO.0000000000000307DOI Listing
March 2017
11 Reads

Genetics of β-Amyloid Precursor Protein in Alzheimer's Disease.

Cold Spring Harb Perspect Med 2017 Jun 1;7(6). Epub 2017 Jun 1.

Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York 10029.

Alzheimer's disease (AD) is characterized neuropathologically by neuronal cell loss, extracellular neuritic plaques composed of β-amyloid (Aβ), and intracellular neurofibrillary tangles composed of hyperphosphorylated tau protein. Aβ is generated by proteolytic processing of the β-amyloid precursor protein (APP). Most individuals with Down syndrome (DS) have three copies of , leading to elevated APP expression, increased Aβ deposition, and characteristic AD neuropathology. Read More

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http://dx.doi.org/10.1101/cshperspect.a024539DOI Listing
June 2017
6 Reads

Down Syndrome, Partial Trisomy 21, and Absence of Alzheimer's Disease: The Role of APP.

J Alzheimers Dis 2017 ;56(2):459-470

Department of Pediatrics, University of California, Irvine Medical Center, Orange, CA, USA.

Overexpression of the amyloid precursor protein (APP) gene on chromosome 21 in Down syndrome (DS) has been linked to increased brain amyloid levels and early-onset Alzheimer's disease (AD). An elderly man with phenotypic DS and partial trisomy of chromosome 21 (PT21) lacked triplication of APP affording an opportunity to study the role of this gene in the pathogenesis of dementia. Multidisciplinary studies between ages 66-72 years comprised neuropsychological testing, independent neurological exams, amyloid PET imaging with 11C-Pittsburgh compound-B (PiB), plasma amyloid-β (Aβ) measurements, and a brain autopsy examination. Read More

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http://dx.doi.org/10.3233/JAD-160836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5662115PMC
February 2018
45 Reads

E3 Ligase SCFβTrCP-induced DYRK1A Protein Degradation Is Essential for Cell Cycle Progression in HEK293 Cells.

J Biol Chem 2016 Dec 2;291(51):26399-26409. Epub 2016 Nov 2.

From the Brain Research Institute,

DYRK1A, located on the Down syndrome (DS) critical region of chromosome 21, was found to be overexpressed in brains of DS and Alzheimer's disease individuals. DYRK1A was considered to play important roles in the pathogenesis of DS and Alzheimer's disease; however, the degradation mechanism of DYRK1A was still unclear. In this study, we found that DYRK1A was degraded through the ubiquitin-proteasome pathway in HEK293 cells. Read More

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http://dx.doi.org/10.1074/jbc.M116.717553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5159501PMC
December 2016
26 Reads

Neuronal exosomes reveal Alzheimer's disease biomarkers in Down syndrome.

Alzheimers Dement 2017 May 15;13(5):541-549. Epub 2016 Oct 15.

Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA; The Knoebel Institute for Healthy Aging, University of Denver, Denver, CO, USA; The Center on Aging, Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA; Center for Alzheimer Research, Karolinska Institutet, Huddinge, Sweden. Electronic address:

Introduction: Individuals with Down syndrome (DS) exhibit Alzheimer's disease (AD) neuropathology and dementia early in life. Blood biomarkers of AD neuropathology would be valuable, as non-AD intellectual disabilities of DS and AD dementia overlap clinically. We hypothesized that elevations of amyloid β (Aβ) peptides and phosphorylated-tau in neuronal exosomes may document preclinical AD. Read More

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http://dx.doi.org/10.1016/j.jalz.2016.08.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5812672PMC
May 2017
48 Reads
10 Citations
12.410 Impact Factor

Towards onset prevention of cognition decline in adults with Down syndrome (The TOP-COG study): A pilot randomised controlled trial.

Trials 2016 07 29;17:370. Epub 2016 Jul 29.

Gordon F Cheesbrough Research Chair and Director of UTOPIAN, University of Toronto, North York General Hospital, 4001 Leslie Street, Toronto, ON, M2K 1E1, Canada.

Background: Dementia is very common in Down syndrome (trisomy 21) adults. Statins may slow brain amyloid β (Aβ, coded on chromosome 21) deposition and, therefore, delay Alzheimer disease onset. One prospective cohort study with Down syndrome adults found participants on statins had reduced risk of incident dementia, but there are no randomised controlled trials (RCTs) on this issue. Read More

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http://dx.doi.org/10.1186/s13063-016-1370-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4966871PMC
July 2016
29 Reads

An inflammatory and trophic disconnect biomarker profile revealed in Down syndrome plasma: Relation to cognitive decline and longitudinal evaluation.

Alzheimers Dement 2016 11 21;12(11):1132-1148. Epub 2016 Jul 21.

Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada; Department of Neurology and Neurosurgery, McGill University, Montreal, Canada; Department of Anatomy and Cell Biology, McGill University, Montreal, Canada. Electronic address:

Introduction: Given that Alzheimer's pathology develops silently over decades in Down syndrome (DS), prognostic biomarkers of dementia are a major need.

Methods: We investigated the plasma levels of Aβ, proNGF, tPA, neuroserpin, metallo-proteases and inflammatory molecules in 31 individuals with DS (with and without dementia) and in 31 healthy controls. We examined associations between biomarkers and cognitive decline. Read More

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http://dx.doi.org/10.1016/j.jalz.2016.05.001DOI Listing
November 2016
36 Reads

Improving Memory and Cognition in Individuals with Down Syndrome.

Authors:
Michael S Rafii

CNS Drugs 2016 07;30(7):567-73

Department of Neurosciences, University of California, San Diego, 9500 Gilman Drive #0949, La Jolla, CA, 92093-0949, USA.

Down syndrome (DS), often due to trisomy 21, is the most common genetic cause of intellectual disability (ID). In addition, virtually all individuals with DS develop the neuropathology of Alzheimer's disease (AD) by the age of 40 years and almost 60 % will manifest symptoms of AD dementia by the age of 65 years. Currently, there are no pharmacological treatments available for ID in individuals with DS and only limited symptomatic treatments for AD dementia. Read More

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http://dx.doi.org/10.1007/s40263-016-0353-4DOI Listing
July 2016
6 Reads

Vitamin E in aging persons with Down syndrome: A randomized, placebo-controlled clinical trial.

Neurology 2016 May 4;86(22):2071-6. Epub 2016 May 4.

From the Department of Psychiatry (M.S.), Alzheimer Disease Research Center, Icahn School of Medicine at Mount Sinai, New York; James J. Peters VAMC (M.S.), Bronx, NY; Alzheimer's Therapeutic Research Institute (P.S.A.), University of Southern California, San Diego; Data Coordinating Center (H.F.A.), New York State Psychiatric Institute; Department of Psychiatry (H.F.A.) and Division of Biostatistics (W.-Y.T.), Columbia University College of Physicians and Surgeons, New York, NY; Department of Neurology (F.L.), McLean Hospital, Belmont; Harvard Medical School (F.L.), Boston, MA; and Center for Aging Studies (A.J.D.), George Jervis Clinic, New York State Institute for Basic Research in Developmental Disabilities, Staten Island.

Objective: To determine whether vitamin E would slow the progression of cognitive deterioration and dementia in aging persons with Down syndrome (DS).

Methods: A randomized, double-blind controlled clinical trial was conducted at 21 clinical sites, and researchers trained in research procedures recruited adults with DS older than 50 years to participate. Participants were randomly assigned to receive 1,000 IU of vitamin E orally twice daily for 3 years or identical placebo. Read More

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http://dx.doi.org/10.1212/WNL.0000000000002714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4891209PMC
May 2016
36 Reads

A Link Between Nerve Growth Factor Metabolic Deregulation and Amyloid-β-Driven Inflammation in Down Syndrome.

CNS Neurol Disord Drug Targets 2016 ;15(4):434-47

Department of Pharmacology and Therapeutics, Faculty of Medicine, McGill University, 3655 Sir- William-Osler Promenade, Room 1210, Montreal, QC, H3G 1Y6, Canada.

In Alzheimer's disease and Down syndrome, cholinergic neurons of the basal forebrain progressively degenerate. This neurotransmitter system is the main source of acetylcholine to the cortex and hippocampus. In the mature and fully differentiated central nervous system, the phenotype of forebrain cholinergic neurons and their nerve terminals in cortex and hippocampus depend on the continuous endogenous supply of nerve growth factor (NGF). Read More

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December 2016
10 Reads

Gait dyspraxia as a clinical marker of cognitive decline in Down syndrome: A review of theory and proposed mechanisms.

Brain Cogn 2016 Apr 27;104:48-57. Epub 2016 Feb 27.

University of Florida College of Medicine, Department of Neurology, Room L3-100, McKnight Brain Institute, 1149 Newell Drive, Gainesville, FL 32611, United States. Electronic address:

Down syndrome (DS) is the most common genetic cause of intellectual disability in children. With aging, DS is associated with an increased risk for Alzheimer's disease (AD). The development of AD neuropathology in individuals with DS can result in further disturbances in cognition and behavior and may significantly exacerbate caregiver burden. Read More

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http://dx.doi.org/10.1016/j.bandc.2016.02.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4801771PMC
April 2016
36 Reads

Frontal Lobe Degeneration in Adults with Down Syndrome and Alzheimer's Disease: A Review.

Dement Geriatr Cogn Disord 2016 19;41(3-4):123-36. Epub 2016 Feb 19.

Old Age Research Group (PROTER), University of Sx00E3;o Paulo School of Medicine, Sx00E3;o Paulo, Brazil.

Background: There is a proven link between Down syndrome and the early development of the neuropathological features of Alzheimer's disease (AD). Changes in the personality and behavior of adults with Down syndrome might indicate the early stages of dementia or of frontotemporal lobar degeneration. The objective of this study was to investigate the executive functions and changes in behavior associated with frontal lobe degeneration in individuals with Down syndrome who develop AD. Read More

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http://dx.doi.org/10.1159/000442941DOI Listing
September 2017
18 Reads