362 results match your criteria Alzheimer Disease In Individuals With Down Syndrome


Cerebrospinal fluid biomarkers of Alzheimer's disease in a cohort of adults with Down syndrome.

Alzheimers Dement (Amst) 2020 9;12(1):e12057. Epub 2020 Jul 9.

Department of Neurology Washington University in St. Louis School of Medicine St. Louis Missouri USA.

Introduction: Virtually all individuals with Down syndrome (DS) will develop Alzheimer's disease (AD) pathology by age 40. Cerebrospinal fluid (CSF) biomarkers have characterized AD pathology in cohorts of late-onset AD (LOAD) and autosomal-dominant AD (ADAD). Few studies have evaluated such biomarkers in adults with DS. Read More

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http://dx.doi.org/10.1002/dad2.12057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7346867PMC

Promising outcome measures of early Alzheimer's dementia in adults with Down syndrome.

Alzheimers Dement (Amst) 2020 5;12(1):e12044. Epub 2020 Jul 5.

Department of Epidemiology School of Public Health Columbia University New York New York USA.

Introduction: Adults with Down syndrome (DS) are at high risk for developing Alzheimer's disease (AD) and its associated dementia, warranting the development of strategies to improve early detection when prevention is possible.

Methods: Using a broad battery of neuropsychological assessments, informant interviews, and clinical record review, we evaluated the psychometrics of measures in a large sample of 561 adults with DS. We tracked longitudinal stability or decline in functioning in a subsample of 269 participants over a period of 3 years, all initially without indications of clinically significant aging-related decline. Read More

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http://dx.doi.org/10.1002/dad2.12044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335903PMC

The promotion of physical activity for the prevention of Alzheimer's disease in adults with Down Syndrome: Rationale and design for a 12 Month randomized trial.

Contemp Clin Trials Commun 2020 Sep 30;19:100607. Epub 2020 Jun 30.

Department of Internal Medicine, The University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS, 66160, USA.

Nearly all individuals with Down Syndrome (DS) display pathology associated with Alzheimer's disease (AD) beginning as early as age 30. Previous research in typically developed adults suggests that increased moderate-to-vigorous physical activity (MVPA) may improve cognitive function and protect against age-related structural and functional changes in the brain; however, the potential impact of increased MVPA on the development of AD in adults with DS has not been evaluated. Despite the potential positive impact of MVPA on cognition and AD risk, participation in MVPA among young adults with DS is low. Read More

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http://dx.doi.org/10.1016/j.conctc.2020.100607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334572PMC
September 2020

Down syndrome: A curative prospect?

Authors:
Jean A Rondal

AIMS Neurosci 2020 22;7(2):168-193. Epub 2020 Jun 22.

University of Liège, Cognitive Sciences, Building 32, Sart Tilman, Liège 4000, Belgium.

Experimental work regarding corrective actions on chromosomes and genes, and control of gene products is yielding promising results. It opens the way to advances in dealing with the etiological aspects of Down syndrome and may lead to important changes in the life of individuals affected with this condition. A small number of molecules are being investigated in pharmacological research that may have positive effects on intellectual functioning. Read More

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http://dx.doi.org/10.3934/Neuroscience.2020012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7321764PMC

Further understanding the connection between Alzheimer's disease and Down syndrome.

Alzheimers Dement 2020 07 16;16(7):1065-1077. Epub 2020 Jun 16.

Alzheimer's Therapeutics Research Institute and Department of Neurology, University of Southern California, Los Angeles, California, USA.

Improved medical care of individuals with Down syndrome (DS) has led to an increase in life expectancy to over the age of 60 years. In conjunction, there has been an increase in age-related co-occurring conditions including Alzheimer's disease (AD). Understanding the factors that underlie symptom and age of clinical presentation of dementia in people with DS may provide insights into the mechanisms of sporadic and DS-associated AD (DS-AD). Read More

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http://dx.doi.org/10.1002/alz.12112DOI Listing

Amyloid accumulation in Down syndrome measured with amyloid load.

Alzheimers Dement (Amst) 2020 16;12(1):e12020. Epub 2020 Apr 16.

University of Wisconsin-Madison Waisman Center Madison Wisconsin.

Introduction: Individuals with Down syndrome (DS) show enhanced amyloid beta (Aβ) deposition in the brain. A new positron emission tomography (PET) index of amyloid load ( ) was recently developed as an alternative to standardized uptake value ratios (SUVrs) to quantify Aβ burden with high sensitivity for detecting and tracking Aβ change.. Read More

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http://dx.doi.org/10.1002/dad2.12020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7233422PMC

Metabolic correlates of prevalent mild cognitive impairment and Alzheimer's disease in adults with Down syndrome.

Alzheimers Dement (Amst) 2020 5;12(1):e12028. Epub 2020 Apr 5.

Taub Institute for Research in Alzheimer's Disease and the Aging Brain Columbia University New York New York USA.

Introduction: Disruption of metabolic function is a recognized feature of late onset Alzheimer's disease (LOAD). We sought to determine whether similar metabolic pathways are implicated in adults with Down syndrome (DS) who have increased risk for Alzheimer's disease (AD).

Methods: We examined peripheral blood from 292 participants with DS who completed baseline assessments in the Alzheimer's Biomarkers Consortium-Down Syndrome (ABC-DS) using untargeted mass spectrometry (MS). Read More

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http://dx.doi.org/10.1002/dad2.12028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7131985PMC

Novel monoclonal antibody 3B8 specifically recognizes pyroglutamate-modified amyloid β 3-42 peptide in brain of AD patients and 3xTg-AD transgenic mice.

Neurosci Lett 2020 Apr 27;724:134876. Epub 2020 Feb 27.

Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (UNAM), Apartado Postal 70228, Cuidad Universitaria, CDMX, CP, 04510, Mexico. Electronic address:

In addition to the full-length beta-amyloid peptides (Aβ 1-40/42), several Aβ variants, truncated at their N- or C-termini and bearing different post-translational modifications, have been detected in the brain of Alzheimer´s disease (AD) patients. AβN3(pE), an Aβ peptide bearing an amino-terminal pyroglutamate at position 3, is a significant constituent of intracellular, extracellular and vascular Aβ deposits in brain tissue from individuals with AD and Down syndrome. Pioneering immunotherapy studies have primarily focused on the full-length Aβ peptide, disregarding the presence of N-truncated/modified species. Read More

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http://dx.doi.org/10.1016/j.neulet.2020.134876DOI Listing

The Search for Biomarkers of Alzheimer's Disease in Down Syndrome.

Am J Intellect Dev Disabil 2020 03;125(2):97-99

Benjamin L. Handen, Western Psychiatric Hospital, Pittsburgh, PA.

Adults with Down syndrome are at high risk for Alzheimer's disease (AD), with most individuals developing clinical dementia by their late 60s. This increased risk for AD has been attributed, at least in part, to triplication and overexpression of the gene for amyloid precursor protein (APP) on chromosome 21 leading to elevated levels of amyloid β peptides. This article offers a brief overview of our current knowledge of AD in the DS population. Read More

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http://dx.doi.org/10.1352/1944-7558-125.2.97DOI Listing

Focusing on cellular biomarkers: The endo-lysosomal pathway in Down syndrome.

Prog Brain Res 2020 20;251:209-243. Epub 2019 Nov 20.

Institut du Cerveau et de la Moelle épinière (ICM), CNRS UMR7225, INSERM U1127, Sorbonne Université, Hôpital de la Pitié-Salpêtrière, Paris, France. Electronic address:

Down syndrome (DS) is the most frequent chromosomal disorder. It is caused by the triplication of human chromosome 21, leading to increased dosage of a variety of genes including APP (Amyloid Precursor Protein). Mainly for this reason, individuals with DS are at high risk to develop Alzheimer's disease (AD). Read More

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http://dx.doi.org/10.1016/bs.pbr.2019.10.002DOI Listing
November 2019

Down syndrome.

Nat Rev Dis Primers 2020 02 6;6(1). Epub 2020 Feb 6.

Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Trisomy 21, the presence of a supernumerary chromosome 21, results in a collection of clinical features commonly known as Down syndrome (DS). DS is among the most genetically complex of the conditions that are compatible with human survival post-term, and the most frequent survivable autosomal aneuploidy. Mouse models of DS, involving trisomy of all or part of human chromosome 21 or orthologous mouse genomic regions, are providing valuable insights into the contribution of triplicated genes or groups of genes to the many clinical manifestations in DS. Read More

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http://dx.doi.org/10.1038/s41572-019-0143-7DOI Listing
February 2020

RvE1 treatment prevents memory loss and neuroinflammation in the Ts65Dn mouse model of Down syndrome.

Glia 2020 Jul 16;68(7):1347-1360. Epub 2020 Jan 16.

Department of Neurobiology, Care Sciences and Society, Division of Neurogeriatrics, Center for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden.

Inflammation can be resolved by pro-homeostatic lipids called specialized pro-resolving mediators (SPMs) upon activation of their receptors. Dysfunctional inflammatory resolution is now considered as a driver of chronic neuroinflammation and Alzheimer's disease (AD) pathogenesis. We have previously shown that SPM levels were reduced and also that SPM-binding receptors were increased in patients with AD compared to age-matched controls. Read More

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http://dx.doi.org/10.1002/glia.23779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7205572PMC

Methylomic profiling in trisomy 21 identifies cognition- and Alzheimer's disease-related dysregulation.

Clin Epigenetics 2019 12 16;11(1):195. Epub 2019 Dec 16.

Institut Jérôme Lejeune, CRB BioJeL, 37 rue des Volontaires, Paris, France.

Background: Trisomy 21 (T21) is associated with intellectual disability that ranges from mild to profound with an average intellectual quotient of around 50. Furthermore, T21 patients have a high risk of developing Alzheimer's disease (AD) early in life, characterized by the presence of senile plaques of amyloid protein and neurofibrillary tangles, leading to neuronal loss and cognitive decline. We postulate that epigenetic factors contribute to the observed variability in intellectual disability, as well as at the level of neurodegeneration seen in T21 individuals. Read More

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http://dx.doi.org/10.1186/s13148-019-0787-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6916110PMC
December 2019

Adaptation of the Clinical Dementia Rating Scale for adults with Down syndrome.

J Neurodev Disord 2019 12 16;11(1):39. Epub 2019 Dec 16.

Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.

Background: Adults with Down syndrome (DS) are at increased risk for Alzheimer disease dementia, and there is a pressing need for the development of assessment instruments that differentiate chronic cognitive impairment, acute neuropsychiatric symptomatology, and dementia in this population of patients.

Methods: We adapted a widely used instrument, the Clinical Dementia Rating (CDR) Scale, which is a component of the Uniform Data Set used by all federally funded Alzheimer Disease Centers for use in adults with DS, and tested the instrument among 34 DS patients recruited from the community. The participants were assessed using two versions of the modified CDR-a caregiver questionnaire and an in-person interview involving both the caregiver and the DS adult. Read More

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http://dx.doi.org/10.1186/s11689-019-9300-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912998PMC
December 2019

[Copper accumulation in the brain of Down syndrome model mice and its pathophysiological significance].

Nihon Yakurigaku Zasshi 2019 ;154(6):335-339

Department of Pathological Biochemistry, Kyoto Pharmaceutical University.

Down syndrome caused by triplication of human chromosome 21 (HSA21) is the most frequent aneuploidy, resulting in mental retardation, intellectual disability and accelerated aging. Individuals with DS are at an increased risk of developing Alzheimer's disease (AD)-like dementia, with up to 75% of DS people in their 60s developing dementia. Oxidative stress is widely accepted as a mechanism underlying a number of DS symptoms, such as accelerated aging and cognitive decline. Read More

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http://dx.doi.org/10.1254/fpj.154.335DOI Listing
December 2019

Down syndrome.

Handb Clin Neurol 2019 ;167:321-336

Department of Neurosciences, University of California San Diego, La Jolla, CA, United States. Electronic address:

Down syndrome (DS; Trisomy 21) is the most common chromosomal disorder in humans. It has numerous associated neurologic phenotypes including intellectual disability, sleep apnea, seizures, behavioral problems, and dementia. With improved access to medical care, people with DS are living longer than ever before. Read More

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http://dx.doi.org/10.1016/B978-0-12-804766-8.00017-0DOI Listing

Inhibitory designer receptors aggravate memory loss in a mouse model of down syndrome.

Neurobiol Dis 2020 02 31;134:104616. Epub 2019 Oct 31.

Knoebel Institute for Healthy Aging, University of Denver, Denver, CO 80208, USA.

The pontine nucleus locus coeruleus (LC) is the primary source of noradrenergic (NE) projections to the brain and is important for working memory, attention, and cognitive flexibility. Individuals with Down syndrome (DS) develop Alzheimer's disease (AD) with high penetrance and often exhibit working memory deficits coupled with degeneration of LC-NE neurons early in the progression of AD pathology. Designer receptors exclusively activated by designer drugs (DREADDs) are chemogenetic tools that allow targeted manipulation of discrete neuronal populations in the brain without the confounds of off-target effects. Read More

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http://dx.doi.org/10.1016/j.nbd.2019.104616DOI Listing
February 2020
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Epidemiology of Dementia and Alzheimer Disease in Individuals With Down Syndrome.

JAMA Neurol 2019 Oct 28. Epub 2019 Oct 28.

Waisman Center, University of Wisconsin-Madison, Madison.

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http://dx.doi.org/10.1001/jamaneurol.2019.3666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6820036PMC
October 2019
1 Read

Alzheimer's disease development in adults with Down syndrome: Caregivers' perspectives.

Am J Med Genet A 2020 01 22;182(1):104-114. Epub 2019 Oct 22.

Genetic Counseling Graduate Program, Division of Human Genetics, The Ohio State University, Columbus, Ohio.

Research about Alzheimer's disease (AD) in individuals with Down syndrome (DS) has predominantly focused on the underlying genetics and neuropathology. Few studies have addressed how AD risk impacts caregivers of adults with DS. This study aimed to explore the perceived impact of AD development in adults with DS on caregivers by assessing caregiver knowledge, concerns, effect on personal life, and resource utilization via a 40-question (maximum) online survey. Read More

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http://dx.doi.org/10.1002/ajmg.a.61390DOI Listing
January 2020
1 Read

Neuropsychological and neurophysiological characterization of mild cognitive impairment and Alzheimer's disease in Down syndrome.

Neurobiol Aging 2019 12 3;84:70-79. Epub 2019 Aug 3.

Center for Biomedical Technology, Laboratory of Cognitive and Computational Neuroscience, Technical University of Madrid, Campus Montegancedo, Madrid, Spain; Department of Legal Medicine, Psychiatry and Pathology, Complutense University of Madrid, Spain, Madrid, Spain.

Down syndrome (DS) has been considered a unique model for the investigation of Alzheimer's disease (AD) but intermediate stages in the continuum are poorly defined. Considering this, we investigated the neurophysiological (i.e. Read More

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http://dx.doi.org/10.1016/j.neurobiolaging.2019.07.017DOI Listing
December 2019
2 Reads

Plasma metabolites related to cellular energy metabolism are altered in adults with Down syndrome and Alzheimer's disease.

Dev Neurobiol 2019 07 26;79(7):622-638. Epub 2019 Aug 26.

Department of Neurology, The University of California, Irvine, Irvine, California.

Down syndrome (DS) is a well-known neurodevelopmental disorder most commonly caused by trisomy of chromosome 21. Because individuals with DS almost universally develop heavy amyloid burden and Alzheimer's disease (AD), biomarker discovery in this population may be extremely fruitful. Moreover, any AD biomarker in DS that does not directly involve amyloid pathology may be of high value for understanding broader mechanisms of AD generalizable to the neurotypical population. Read More

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http://dx.doi.org/10.1002/dneu.22716DOI Listing
July 2019
4 Reads

Synaptic actin stabilization protein loss in Down syndrome and Alzheimer disease.

Brain Pathol 2020 03 8;30(2):319-331. Epub 2019 Sep 8.

Department of Anatomy & Neurobiology, University of California at Irvine, Irvine, CA, 92697-1275.

Reduced spine densities and age-dependent accumulation of amyloid β and tau pathology are shared features of Down syndrome (DS) and Alzheimer's disease (AD). Both spine morphology and the synaptic plasticity that supports learning depend upon the actin cytoskeleton, suggesting that disturbances in actin regulatory signaling might underlie spine defects in both disorders. The present study evaluated the synaptic levels of two proteins that promote filamentous actin stabilization, the Rho GTPase effector p21-activated kinase 3 (PAK3) and Arp2, in DS vs. Read More

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http://dx.doi.org/10.1111/bpa.12779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7015764PMC
March 2020
4 Reads

Blood-based biomarkers for Down syndrome and Alzheimer's disease: A systematic review.

Dev Neurobiol 2019 07 3;79(7):699-710. Epub 2019 Sep 3.

Department of Pharmacology & Neuroscience, Institute for Translational Research, University of North Texas Health Science Center, Fort Worth, Texas.

Down syndrome (DS) occurs due to triplication of chromosome 21. Individuals with DS face an elevated risk for development of Alzheimer's disease (AD) due to increased amyloid beta (Aβ) resulting from the over-expression of the amyloid precursor protein found on chromosome 21. Diagnosis of AD among individuals with DS poses particular challenges resulting in an increased focus on alternative diagnostic methods such as blood-based biomarkers. Read More

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http://dx.doi.org/10.1002/dneu.22714DOI Listing
July 2019
5 Reads

Plasma amyloid and tau as dementia biomarkers in Down syndrome: Systematic review and meta-analyses.

Dev Neurobiol 2019 07 11;79(7):684-698. Epub 2019 Sep 11.

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

Individuals with Down syndrome (DS) are at high risk of developing Alzheimer's disease (AD). Discovering reliable biomarkers which could facilitate early AD diagnosis and be used to predict/monitor disease course would be extremely valuable. To examine if analytes in blood related to amyloid plaques may constitute such biomarkers, we conducted meta-analyses of studies comparing plasma amyloid beta (Aβ) levels between DS individuals and controls, and between DS individuals with and without dementia. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/dneu.22715
Publisher Site
http://dx.doi.org/10.1002/dneu.22715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6790908PMC
July 2019
7 Reads

Exosome release and cargo in Down syndrome.

Dev Neurobiol 2019 07 6;79(7):639-655. Epub 2019 Aug 6.

Department of Biological Sciences and the Knoebel Institute for Healthy Aging, University of Denver, Denver, Colorado.

Down syndrome (DS) is a multisystem disorder affecting 1 in 800 births worldwide. Advancing technology, medical treatment, and social intervention have dramatically increased life expectancy, yet there are many etiologies of this disorder that are in need of further research. The advent of the ability to capture extracellular vesicles (EVs) in blood from specific cell types allows for the investigation of novel intracellular processes. Read More

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http://dx.doi.org/10.1002/dneu.22712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388580PMC
July 2019
9 Reads

Lysosomal Dysfunction in Down Syndrome Is APP-Dependent and Mediated by APP-βCTF (C99).

J Neurosci 2019 07 1;39(27):5255-5268. Epub 2019 May 1.

Center for Dementia Research, Nathan Kline Institute for Psychiatric Research, Orangeburg, New York, 10962,

Lysosomal failure underlies pathogenesis of numerous congenital neurodegenerative disorders and is an early and progressive feature of Alzheimer's disease (AD) pathogenesis. Here, we report that lysosomal dysfunction in Down ayndrome (trisomy 21), a neurodevelopmental disorder and form of early onset AD, requires the extra gene copy of amyloid precursor protein (APP) and is specifically mediated by the β cleaved carboxy terminal fragment of APP (APP-βCTF, C99). In primary fibroblasts from individuals with DS, lysosomal degradation of autophagic and endocytic substrates is selectively impaired, causing them to accumulate in enlarged autolysosomes/lysosomes. Read More

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http://www.jneurosci.org/lookup/doi/10.1523/JNEUROSCI.0578-1
Publisher Site
http://dx.doi.org/10.1523/JNEUROSCI.0578-19.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6607756PMC
July 2019
8 Reads

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

Neurobiol Aging 2019 06 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
June 2019
28 Reads

Novel tau filament fold in chronic traumatic encephalopathy encloses hydrophobic molecules.

Nature 2019 04 20;568(7752):420-423. Epub 2019 Mar 20.

MRC Laboratory of Molecular Biology, Cambridge, UK.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy that is associated with repetitive head impacts or exposure to blast waves. First described as punch-drunk syndrome and dementia pugilistica in retired boxers, CTE has since been identified in former participants of other contact sports, ex-military personnel and after physical abuse. No disease-modifying therapies currently exist, and diagnosis requires an autopsy. Read More

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http://dx.doi.org/10.1038/s41586-019-1026-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6472968PMC
April 2019
16 Reads

Targeting the Iron-Response Elements of the mRNAs for the Alzheimer's Amyloid Precursor Protein and Ferritin to Treat Acute Lead and Manganese Neurotoxicity.

Int J Mol Sci 2019 Feb 25;20(4). Epub 2019 Feb 25.

Neurochemistry Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.

The therapeutic value of inhibiting translation of the amyloid precursor protein (APP) offers the possibility to reduce neurotoxic amyloid formation, particularly in cases of familial Alzheimer's disease (AD) caused by APP gene duplications (Dup⁻APP) and in aging Down syndrome individuals. APP mRNA translation inhibitors such as the anticholinesterase phenserine, and high throughput screened molecules, selectively inhibited the uniquely folded iron-response element (IRE) sequences in the 5'untranslated region (5'UTR) of APP mRNA and this class of drug continues to be tested in a clinical trial as an anti-amyloid treatment for AD. By contrast, in younger age groups, APP expression is not associated with amyloidosis, instead it acts solely as a neuroprotectant while facilitating cellular ferroportin-dependent iron efflux. Read More

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http://dx.doi.org/10.3390/ijms20040994DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412244PMC
February 2019
29 Reads
2.862 Impact Factor

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 06 27;63(6):614-623. 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
June 2019
15 Reads

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

Nat Rev Neurol 2019 03;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
29 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
35 Reads

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

Alzheimers Dement 2019 02 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
17 Reads

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

JAMA Neurol 2019 02;76(2):152-160

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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6439956PMC
February 2019
39 Reads

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

JAMA Neurol 2019 02;76(2):142-143

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
February 2019
8 Reads

Microbleeds and Cerebral Amyloid Angiopathy in the Brains of People with Down Syndrome with Alzheimer's Disease.

J Alzheimers Dis 2019 ;67(1):103-112

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

Cerebrovascular pathology is a significant mediator in Alzheimer's disease (AD) in the general population. In people with Down syndrome (DS), the contribution of vascular pathology to dementia may play a similar role in age of onset and/or the rate of progression of AD. In the current study, we explored the extent of microbleeds (MBs) and the link between cerebral amyloid angiopathy (CAA) and MBs in the frontal cortex (FCTX) and occipital cortex (OCTX) in an autopsy series from individuals with DS (<40 years), DS with AD pathology (DSAD), sporadic AD, and control cases (2-83 years). Read More

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http://dx.doi.org/10.3233/JAD-180589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6424116PMC
March 2020
31 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
34 Reads

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

Brain Behav Immun 2019 01 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
Publisher Site
http://dx.doi.org/10.1016/j.bbi.2018.10.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358279PMC
January 2019
32 Reads

Comparison of longitudinal Aβ in nondemented elderly and Down syndrome.

Neurobiol Aging 2019 01 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
Publisher Site
http://dx.doi.org/10.1016/j.neurobiolaging.2018.09.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251757PMC
January 2019
19 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
19 Reads

Modeling amyloid beta and tau pathology in human cerebral organoids.

Mol Psychiatry 2018 12 31;23(12):2363-2374. Epub 2018 Aug 31.

Mitchell Center for Alzheimer's Disease and Related Brain Disorders. Department of Neurology, University of Texas Medical School at Houston, Houston, TX, USA.

The typical abnormalities observed in the brain of Alzheimer's disease (AD) patients include synaptic alterations, neuronal death, brain inflammation, and the accumulation of protein aggregates in the form of amyloid plaques and neurofibrillary tangles. Despite the development of many animal and in vitro models for AD, there is a lack of an experimental approach that fully recapitulates essential aspects of the disease in human cells. Here, we report the generation of a new model to study AD, consisting of cerebral organoids (COs) produced from human-induced pluripotent stem cells (iPSCs). Read More

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http://dx.doi.org/10.1038/s41380-018-0229-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6594704PMC
December 2018
26 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
30 Reads

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

JAMA Neurol 2018 11;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
52 Reads

The age of onset and evolution of Braak tangle stage and Thal amyloid pathology of Alzheimer's disease in individuals with Down syndrome.

Acta Neuropathol Commun 2018 07 4;6(1):56. Epub 2018 Jul 4.

Institute of Brain, Behaviour and Mental Health, Faculty of Medical and Human Sciences University of Manchester, Salford Royal Hospital, Stott Lane, Salford, M6 8HD, England.

While post mortem studies have identified the major cell types and functional systems affected in Alzheimer's disease (AD) the initial sites and molecular characteristics of pathology are still unclear. Because individuals with Down syndrome (DS) (trisomy 21) develop the full pathological changes of AD in a predictable way by the time they reach middle to late age, a study of the brains of such persons at different ages makes an ideal 'model system' in which the sites of earliest onset of pathology can be detected and the subsequent progression of changes be monitored. In the present study we have examined the brains of 56 individuals with DS ranging from new-born to 76 years for the presence of amyloid and tau pathology in key cortical and subcortical regions. Read More

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http://dx.doi.org/10.1186/s40478-018-0559-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6030772PMC
July 2018
20 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
12 Reads

Trisomy of human chromosome 21 enhances amyloid-β deposition independently of an extra copy of APP.

Brain 2018 08;141(8):2457-2474

Department of Neurodegenerative Disease, UCL Institute of Neurology, London, WC1N 3BG UK.

Down syndrome, caused by trisomy of chromosome 21, is the single most common risk factor for early-onset Alzheimer's disease. Worldwide approximately 6 million people have Down syndrome, and all these individuals will develop the hallmark amyloid plaques and neurofibrillary tangles of Alzheimer's disease by the age of 40 and the vast majority will go on to develop dementia. Triplication of APP, a gene on chromosome 21, is sufficient to cause early-onset Alzheimer's disease in the absence of Down syndrome. Read More

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http://dx.doi.org/10.1093/brain/awy159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6061702PMC
August 2018
37 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
13 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
49 Reads

Patterns and severity of vascular amyloid in Alzheimer's disease associated with duplications and missense mutations in APP gene, Down syndrome and sporadic Alzheimer's disease.

Acta Neuropathol 2018 10 16;136(4):569-587. Epub 2018 May 16.

Institute of Psychiatry, Psychology and Neuroscience, King's College London, 16 De Crespigny Park, London, UK.

In this study, we have compared the severity of amyloid plaque formation and cerebral amyloid angiopathy (CAA), and the subtype pattern of CAA pathology itself, between APP genetic causes of AD (APPdup, APP mutations), older individuals with Down syndrome (DS) showing the pathology of Alzheimer's disease (AD) and individuals with sporadic (early and late onset) AD (sEOAD and sLOAD, respectively). The aim of this was to elucidate important group differences and to provide mechanistic insights related to clinical and neuropathological phenotypes. Since lipid and cholesterol metabolism is implicated in AD as well as vascular disease, we additionally aimed to explore the role of APOE genotype in CAA severity and subtypes. Read More

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http://dx.doi.org/10.1007/s00401-018-1866-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6132946PMC
October 2018
35 Reads

Anti-IL17 treatment ameliorates Down syndrome phenotypes in mice.

Brain Behav Immun 2018 10 31;73:235-251. Epub 2018 May 31.

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

Down syndrome (DS) is characterized by structural and functional anomalies that are present prenatally and that lead to intellectual disabilities. Later in life, the cognitive abilities of DS individuals progressively deteriorate due to the development of Alzheimer's disease (AD)-associated neuropathology (i.e. Read More

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http://dx.doi.org/10.1016/j.bbi.2018.05.008DOI Listing
October 2018
7 Reads