296 results match your criteria Alzheimer's Disease and APOE-4


Involvement of Lipids in Alzheimer's Disease Pathology and Potential Therapies.

Front Physiol 2020 9;11:598. Epub 2020 Jun 9.

Huntington Medical Research Institutes, Pasadena, CA, United States.

Lipids constitute the bulk of the dry mass of the brain and have been associated with healthy function as well as the most common pathological conditions of the brain. Demographic factors, genetics, and lifestyles are the major factors that influence lipid metabolism and are also the key components of lipid disruption in Alzheimer's disease (AD). Additionally, the most common genetic risk factor of AD, APOE ϵ4 genotype, is involved in lipid transport and metabolism. Read More

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http://dx.doi.org/10.3389/fphys.2020.00598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7296164PMC

Pharmacogenetic considerations when prescribing cholinesterase inhibitors for the treatment of Alzheimer's disease.

Authors:
Ramón Cacabelos

Expert Opin Drug Metab Toxicol 2020 Jun 23:1-29. Epub 2020 Jun 23.

Department of Genomic Medicine, EuroEspes Biomedical Research Center, International Center of Neuroscience and Genomic Medicine , Bergondo, Corunna, Spain.

Introduction: Cholinergic dysfunction, demonstrated in the late 1970s and early 1980s, led to the introduction of acetylcholinesterase inhibitors (AChEIs) in 1993 (Tacrine) to enhance cholinergic neurotransmission as the first line of treatment against Alzheimer's disease (AD). The new generation of AChEIs, represented by Donepezil (1996), Galantamine (2001) and Rivastigmine (2002), is the only treatment for AD to date, together with Memantine (2003). AChEIs are not devoid of side-effects and their cost-effectiveness is limited. Read More

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http://dx.doi.org/10.1080/17425255.2020.1779700DOI Listing

Effects of sex, age, and apolipoprotein E genotype on hippocampal parenchymal fraction in cognitively normal older adults.

Psychiatry Res Neuroimaging 2020 Jul 14;301:111107. Epub 2020 May 14.

Center for Brain Imaging and Neuromodulation, The Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY, USA.

Early detection of Alzheimer's disease (AD) is important for timely interventions and developing new treatments. Hippocampus atrophy is an early biomarker of AD. The hippocampal parenchymal fraction (HPF) is a promising measure of hippocampal structural integrity computed from structural MRI. Read More

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http://dx.doi.org/10.1016/j.pscychresns.2020.111107DOI Listing

APOE ε4 and the influence of sex, age, vascular risk factors, and ethnicity on cognitive decline.

J Gerontol A Biol Sci Med Sci 2020 May 12. Epub 2020 May 12.

Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia.

We aimed to examine the relationship between APOE*4 carriage on cognitive decline, and whether these associations were moderated by sex, baseline age, ethnicity, and vascular risk factors. Participants were 19,225 individuals aged 54-103 years from 15 longitudinal cohort studies with a mean follow up duration ranging between 1.2 and 10. Read More

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http://dx.doi.org/10.1093/gerona/glaa116DOI Listing

Pharmacogenomics of Cognitive Dysfunction and Neuropsychiatric Disorders in Dementia.

Authors:
Ramon Cacabelos

Int J Mol Sci 2020 Apr 26;21(9). Epub 2020 Apr 26.

EuroEspes Biomedical Research Center, International Center of Neuroscience and Genomic Medicine, 15165-Bergondo, Corunna, Spain.

Symptomatic interventions for patients with dementia involve anti-dementia drugs to improve cognition, psychotropic drugs for the treatment of behavioral disorders (BDs), and different categories of drugs for concomitant disorders. Demented patients may take >6-10 drugs/day with the consequent risk for drug-drug interactions and adverse drug reactions (ADRs >80%) which accelerate cognitive decline. The pharmacoepigenetic machinery is integrated by pathogenic, mechanistic, metabolic, transporter, and pleiotropic genes redundantly and promiscuously regulated by epigenetic mechanisms. Read More

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http://dx.doi.org/10.3390/ijms21093059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246738PMC

Whole-Blood Levels of MicroRNA-9 Are Decreased in Patients With Late-Onset Alzheimer Disease.

Am J Alzheimers Dis Other Demen 2020 Jan-Dec;35:1533317520911573

Medical Faculty, University of Brasília, Brasília, Federal District, Brazil.

Recent evidence suggests changes in circulating microRNA levels may be promising biomarkers for the clinical diagnosis of Alzheimer disease (AD). We hypothesized that whole-blood microRNAs may be useful to identify individuals with established AD. For this purpose, a sample of community-dwelling women (≥55 years old) carrying the ∊4 allele were clinically evaluated using the American Psychiatric Association/, Fourth edition and the Alzheimer Disease Assessment Scale-Cognitive Subscale criteria to diagnose probable AD, and the Clinical Dementia Rating scale to stage the dementia. Read More

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http://dx.doi.org/10.1177/1533317520911573DOI Listing
April 2020
1.426 Impact Factor

Associations of urinary 8-iso-prostaglandin F levels with all-cause dementia, Alzheimer's disease, and vascular dementia incidence: results from a prospective cohort study.

Alzheimers Dement 2020 May 12;16(5):804-813. Epub 2020 Apr 12.

Network Aging Research, Heidelberg University, Heidelberg, Germany.

Introduction: Prospective studies on a potential association of 8-iso-prostaglandin F (8-iso-PGF ) levels, a biomarker of lipid peroxidation, with dementia are limited.

Methods: Multivariate Cox regression models were used to assess potential associations of urinary 8-iso-PGF levels with all-cause, Alzheimer's disease (AD), and vascular dementia (VD) incidence in 5853 older adults from a German, population-based cohort.

Results: Over 14 years of follow-up, 365 all-cause dementia cases including 127 VD and 109 AD cases were diagnosed. Read More

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http://dx.doi.org/10.1002/alz.12081DOI Listing

Effect of APOE Genotype on Plasma Docosahexaenoic Acid (DHA), Eicosapentaenoic Acid, Arachidonic Acid, and Hippocampal Volume in the Alzheimer's Disease Cooperative Study-Sponsored DHA Clinical Trial.

J Alzheimers Dis 2020 ;74(3):975-990

Department of Medicine, University of Southern California, Los Angeles, CA, USA.

Background: Docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (AA) play key roles in several metabolic processes relevant to Alzheimer's disease (AD) pathogenesis and neuroinflammation. Carrying the APOEɛ4 allele (APOE4) accelerates omega-3 polyunsaturated fatty acid (PUFA) oxidation. In a pre-planned subgroup analysis of the Alzheimer's Disease Cooperative Study-sponsored DHA clinical trial, APOE4 carriers with mild probable AD had no improvements in cognitive outcomes compared to placebo, while APOE 4 non-carriers showed a benefit from DHA supplementation. Read More

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http://dx.doi.org/10.3233/JAD-191017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7156328PMC
January 2020

Modelling prognostic trajectories of cognitive decline due to Alzheimer's disease.

Neuroimage Clin 2020 Jan 26;26:102199. Epub 2020 Jan 26.

Department of Psychology, University of Cambridge, Cambridge, United Kingdom. Electronic address:

Alzheimer's disease (AD) is characterised by a dynamic process of neurocognitive changes from normal cognition to mild cognitive impairment (MCI) and progression to dementia. However, not all individuals with MCI develop dementia. Predicting whether individuals with MCI will decline (i. Read More

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http://dx.doi.org/10.1016/j.nicl.2020.102199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044529PMC
January 2020

Alzheimer disease starts in childhood in polluted Metropolitan Mexico City. A major health crisis in progress.

Environ Res 2020 Apr 25;183:109137. Epub 2020 Jan 25.

Interdisciplinary Statistical Research Unit, Indian Statistical Institute, 700108, Kolkata, India.

Exposures to fine particulate matter (PM) and ozone (O) above USEPA standards are associated with Alzheimer's disease (AD) risk. Metropolitan Mexico City (MMC) youth have life time exposures to PM and O above standards. We focused on MMC residents ≤30 years and reviewed 134 consecutive autopsies of subjects age 20. Read More

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http://dx.doi.org/10.1016/j.envres.2020.109137DOI Listing

Interaction effect of alcohol consumption and Alzheimer disease polygenic risk score on the brain cortical thickness of cognitively normal subjects.

Alcohol 2020 Jun 14;85:1-12. Epub 2019 Nov 14.

Laboratory of Neuro Imaging, USC Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, United States. Electronic address:

Alcohol consumption and genetic risk for Alzheimer disease (AD) are among many factors known to be associated with brain structure in cognitively healthy adults. It is unclear, however, whether the effect of alcohol consumption on brain structure varies depending on a person's level of genetic risk for AD. We hypothesized that there is an interaction effect of alcohol consumption and a 33-SNP AD polygenic risk score (PRS) on the cortical thickness of brain regions known to be affected early in the course of AD. Read More

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http://dx.doi.org/10.1016/j.alcohol.2019.11.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220836PMC

The Role of Physical Fitness in Cognitive-Related Biomarkers in Persons at Genetic Risk of Familial Alzheimer's Disease.

J Clin Med 2019 Oct 7;8(10). Epub 2019 Oct 7.

Division of Behavioral Neurology, Department of Neurology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan.

Introduction: Nondemented people with a family history of Alzheimer's disease (ADFH) and the ApoE-4 allele have been demonstrated to show a trend for a higher probability of cognitive decline and aberrant levels of cognitive-related biomarkers. However, the potential interactive effects on physical fitness have not been investigated. The primary purpose of this study was to determine whether ADFH individuals with the ApoE-4 genotype show deviant brain event-related neural oscillatory performance and cognitively-related molecular indices. Read More

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http://dx.doi.org/10.3390/jcm8101639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832576PMC
October 2019
1 Read

Independent and joint effects of vascular and cardiometabolic risk factor pairs for risk of all-cause dementia: a prospective population-based study.

Int Psychogeriatr 2019 10;31(10):1421-1432

Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.

Objectives: To assess independent and joint effects of pairs of vascular and cardiometabolic risk factors (VCMRFs) in relation to risk of all-cause dementia.

Design: Population-based longitudinal cohort study of cognitive impairment. We used an algorithm to select pairs of VCMRFs and tested their joint effects in time-dependent Cox models. Read More

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http://dx.doi.org/10.1017/S1041610219001066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6948010PMC
October 2019

The Influence of Cerebrospinal Fluid Abnormalities and APOE 4 on PHF-Tau Protein: Evidence From Voxel Analysis and Graph Theory.

Front Aging Neurosci 2019 8;11:208. Epub 2019 Aug 8.

School of Information Science and Engineering, Shandong Normal University, Jinan, China.

Mild cognitive impairment (MCI) is a transitional state between the cognitive changes in normal aging and Alzheimer's disease (AD), which induces abnormalities in specific brain regions. Previous studies showed that paired helical filaments Tau (PHF-Tau) protein is a potential pathogenic protein which may cause abnormal brain function and structure in MCI and AD patients. However, the understanding of the PHF-Tau protein network in MCI patients is limited. Read More

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http://dx.doi.org/10.3389/fnagi.2019.00208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6694441PMC
August 2019
3 Reads
2.843 Impact Factor

Determinants of cognitive performance and decline in 20 diverse ethno-regional groups: A COSMIC collaboration cohort study.

PLoS Med 2019 07 23;16(7):e1002853. Epub 2019 Jul 23.

Centre for Healthy Brain Ageing, University of New South Wales, Sydney, New South Wales, Australia.

Background: With no effective treatments for cognitive decline or dementia, improving the evidence base for modifiable risk factors is a research priority. This study investigated associations between risk factors and late-life cognitive decline on a global scale, including comparisons between ethno-regional groups.

Methods And Findings: We harmonized longitudinal data from 20 population-based cohorts from 15 countries over 5 continents, including 48,522 individuals (58. Read More

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http://dx.doi.org/10.1371/journal.pmed.1002853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6650056PMC
July 2019
10 Reads

Altered SPMs and age-associated decrease in brain DHA in female mice.

FASEB J 2019 09 29;33(9):10315-10326. Epub 2019 Jul 29.

Department of Nutrition and Preventive Medicine, Norwich Medical School, University of East Anglia, Norwich, United Kingdom.

An apolipoprotein E () 4 genotype is the most important, common genetic determinant for Alzheimer disease (AD), and female carriers present with an increased risk compared with males. The study quantified cortical and hippocampal fatty acid and phospholipid profiles along with select eicosapentaenoic acid (EPA)- and docosahexaenoic acid (DHA)-derived specialized proresolving mediators (SPMs) in 2-, 9-, and 18-mo-old and male and female mice. A 10% lower cortical DHA was evident in females at 18 mo compared with 2 mo, with no significant decrease in or males. Read More

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http://dx.doi.org/10.1096/fj.201900423RDOI Listing
September 2019
4 Reads

Cyclic O exposure synergizes with aging leading to memory impairment in male APOE ε3, but not APOE ε4, targeted replacement mice.

Neurobiol Aging 2019 09 17;81:9-21. Epub 2019 May 17.

Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address:

The etiology of late-onset Alzheimer's disease is unknown. Recent epidemiological studies suggest that exposure to high levels of ozone (O) may be a risk factor for late-onset Alzheimer's disease. Nonetheless, whether and how O exposure contributes to AD development remains to be determined. Read More

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http://dx.doi.org/10.1016/j.neurobiolaging.2019.05.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6732233PMC
September 2019
8 Reads

Anxiety correlates with cortical surface area in subjective cognitive decline: APOE ε4 carriers versus APOE ε4 non-carriers.

Alzheimers Res Ther 2019 06 3;11(1):50. Epub 2019 Jun 3.

Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China.

Background: Subjective cognitive decline (SCD) is characterized by self-reported cognitive deficits without measurable cognitive impairment. It has been suggested that individuals with SCD exhibited brain structural alterations in widespread cortical thinning or gray matter loss in the medial temporal and frontotemporal regions. Apolipoprotein E (APOE) ε4 allele is thought to be a genetic marker associated with risk of SCD. Read More

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http://dx.doi.org/10.1186/s13195-019-0505-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547570PMC
June 2019
13 Reads

Sirtuins in Alzheimer's Disease: SIRT2-Related GenoPhenotypes and Implications for PharmacoEpiGenetics.

Int J Mol Sci 2019 Mar 12;20(5). Epub 2019 Mar 12.

Department of Psychiatry and Behavioral Science, Stony Brook University, Stony Brook, NY 11794, USA.

Sirtuins (SIRT1-7) are NAD⁺-dependent protein deacetylases/ADP ribosyltransferases with important roles in chromatin silencing, cell cycle regulation, cellular differentiation, cellular stress response, metabolism and aging. Sirtuins are components of the epigenetic machinery, which is disturbed in Alzheimer's disease (AD), contributing to AD pathogenesis. There is an association between the genotype (rs10410544) (50. Read More

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http://dx.doi.org/10.3390/ijms20051249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6429449PMC
March 2019
13 Reads

Analysis of apolipoprotein E genetic polymorphism in a large ethnic Hakka population in southern China.

Genet Mol Biol 2018 Oct-Dec;41(4):742-749. Epub 2018 Nov 29.

Center for Cardiovascular Diseases, Meizhou People's Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, Meizhou Hospital Affiliated to Sun Yat-sen University, Meizhou, P.R. China.

There is currently no data about the genetic variations of APOE in Hakka population in China. The aim of this study was to analyze the allelic and genotypic frequencies of APOE gene polymorphisms in a large ethnic Hakka population in southern China. The APOE genes of 6,907 subjects were genotyped by the gene chip platform. Read More

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http://www.scielo.br/scielo.php?script=sci_arttext&pid=S
Publisher Site
http://dx.doi.org/10.1590/1678-4685-GMB-2017-0301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6415608PMC
November 2018
31 Reads

Longer TOMM40 poly-T variants associated with higher FDDNP-PET medial temporal tau and amyloid binding.

PLoS One 2018 5;13(12):e0208358. Epub 2018 Dec 5.

Department of Psychiatry & Biobehavioral Sciences, Semel Institute for Neuroscience & Human Behavior, David Geffen School of Medicine at UCLA, Los Angeles, United States of America.

Background: The translocase of outer mitochondrial membrane 40 (TOMM40), which lies in linkage disequilibrium with the apolipoprotein E (APOE) gene, has been implicated in Alzheimer's disease (AD). TOMM40 influences AD pathology through mitochondrial neurotoxicity, and the medial temporal lobe (MTL) is the most likely brain region for identifying early manifestations of AD-related morphology changes. While early reports indicated that the longer length poly-T allele of TOMM40 increases risk for AD, these findings have not been consistently replicated in further studies. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0208358PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6281258PMC
May 2019
10 Reads

Apolipoprotein E genotype moderates the association between dietary polyunsaturated fat and brain function: an exploration of cerebral glutamate and cognitive performance.

Nutr Neurosci 2018 Nov 22:1-10. Epub 2018 Nov 22.

a Department of Psychology , The University of Texas at Austin , USA.

Objective: To investigate the effect of Apolipoprotein E (APOE) genotype on the association between dietary polyunsaturated fat (PUFA), cognitive function, and cerebral glutamate.

Methods: A participant sample of 122 middle-aged adults were grouped according to APOE genotype (ϵ4 carrier or ϵ4 non-carrier) and asked to record dietary intake for three consecutive days. All participants also underwent neuropsychological testing and a proton magnetic resonance spectroscopy (H MRS) scan to assess glutamate in the posterior cingulate cortex. Read More

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http://dx.doi.org/10.1080/1028415X.2018.1547857DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6531361PMC
November 2018
14 Reads

Voltammetric determination of the Alzheimer's disease-related ApoE 4 gene from unamplified genomic DNA extracts by ferrocene-capped gold nanoparticles.

Mikrochim Acta 2018 11 14;185(12):549. Epub 2018 Nov 14.

Department oft of Obstetrics and Gynecology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, 410013, People's Republic of China.

A sensitive method is described for detection of the apoE 4 gene detection which is important for early diagnosis of Alzheimer's disease. It is based on signal amplification by using ferrocene (Fc) capped gold nanoparticles modified with streptavidin. The immobilized oligonucleotide probe captures complementary apoE 4 gene. Read More

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http://dx.doi.org/10.1007/s00604-018-3087-9DOI Listing
November 2018
40 Reads

Genome-wide association study of brain amyloid deposition as measured by Pittsburgh Compound-B (PiB)-PET imaging.

Mol Psychiatry 2018 Oct 25. Epub 2018 Oct 25.

Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA.

Deposition of amyloid plaques in the brain is one of the two main pathological hallmarks of Alzheimer's disease (AD). Amyloid positron emission tomography (PET) is a neuroimaging tool that selectively detects in vivo amyloid deposition in the brain and is a reliable endophenotype for AD that complements cerebrospinal fluid biomarkers with regional information. We measured in vivo amyloid deposition in the brains of ~1000 subjects from three collaborative AD centers and ADNI using C-labeled Pittsburgh Compound-B (PiB)-PET imaging followed by meta-analysis of genome-wide association studies, first to our knowledge for PiB-PET, to identify novel genetic loci for this endophenotype. Read More

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http://www.nature.com/articles/s41380-018-0246-7
Publisher Site
http://dx.doi.org/10.1038/s41380-018-0246-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6219464PMC
October 2018
36 Reads

Female Sex and Alzheimer's Risk: The Menopause Connection.

J Prev Alzheimers Dis 2018 ;5(4):225-230

Lisa Mosconi, PhD, Department of Neurology, Weill Cornell Medicine, 428 East 72nd St, Suite 500, Room 407, New York, NY, 10021; Tel: (212) 746-4624, Email:

Along with advanced age and apolipoprotein E (APOE)-4 genotype, female sex is a major risk factor for developing late-onset Alzheimer's disease (AD). Considering that AD pathology begins decades prior to clinical symptoms, the higher risk in women cannot simply be accounted for by their greater longevity as compared to men. Recent investigation into sex-specific pathophysiological mechanisms behind AD risk has implicated the menopause transition (MT), a midlife neuroendocrine transition state unique to females. Read More

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http://dx.doi.org/10.14283/jpad.2018.34DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6198681PMC
November 2019
14 Reads

Role of phosphatidylcholine-DHA in preventing APOE4-associated Alzheimer's disease.

Authors:
Rhonda P Patrick

FASEB J 2019 02 5;33(2):1554-1564. Epub 2018 Oct 5.

University of California San Francisco Benioff, Children's Hospital Oakland Research Institute, Oakland, California, USA.

Dietary and supplemental intake of the ω-3 fatty acid docosahexaenoic acid (DHA) reduces risk of Alzheimer's disease (AD) and ameliorates symptoms. The apolipoprotein E ( APOE) 4 allele is the strongest risk factor for sporadic AD, exclusive of age. APOE4 carriers respond well to the DHA present in fish but do not respond as well to dietary supplements. Read More

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http://dx.doi.org/10.1096/fj.201801412RDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6338661PMC
February 2019
105 Reads

Influence of and on Behavioral and Cognitive Features of Female Patients Affected by Mild Cognitive Impairment or Alzheimer's Disease.

Front Aging Neurosci 2018 13;10:92. Epub 2018 Apr 13.

Department of Neuroscience, Imaging, and Clinical Science, Università degli Studi G. d'Annunzio Chieti e Pescara, Chieti, Italy.

The risk for Alzheimer's disease (AD) is associated with the presence of the 𝜀4 allele of Apolipoprotein E () gene and, recently, with a novel genetic variant of the gene. This study aimed at evaluating interactions between -𝜀4 and /G variants in the modulation of behavioral and cognitive features of two cohorts of patients suffering from mild cognitive impairment (MCI) or AD. We enrolled a total of 173 female MCI or AD patients (83 MCI; 90 AD). Read More

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http://dx.doi.org/10.3389/fnagi.2018.00092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5932379PMC
April 2018
30 Reads

Targeting of nonlipidated, aggregated apoE with antibodies inhibits amyloid accumulation.

J Clin Invest 2018 05 30;128(5):2144-2155. Epub 2018 Mar 30.

Department of Neurology, Hope Center for Neurological Disorders, Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, Missouri, USA.

The apolipoprotein E E4 allele of the APOE gene is the strongest genetic factor for late-onset Alzheimer disease (LOAD). There is compelling evidence that apoE influences Alzheimer disease (AD) in large part by affecting amyloid β (Aβ) aggregation and clearance; however, the molecular mechanism underlying these findings remains largely unknown. Herein, we tested whether anti-human apoE antibodies can decrease Aβ pathology in mice producing both human Aβ and apoE4, and investigated the mechanism underlying these effects. Read More

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http://dx.doi.org/10.1172/JCI96429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5919821PMC
May 2018
37 Reads
3 Citations
13.210 Impact Factor

The clinical significance of plasma clusterin and Aβ in the longitudinal follow-up of patients with Alzheimer's disease.

Alzheimers Res Ther 2017 Nov 23;9(1):91. Epub 2017 Nov 23.

Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.

Background: Clusterin and beta-amyloid (Aβ) are involved in the pathogenesis of Alzheimer's disease (AD). The clinical significance of plasma clusterin and Aβ in AD progression remains controversial.

Methods: We recruited 322 patients with AD and 88 controls between August 2012 and June 2013. Read More

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http://dx.doi.org/10.1186/s13195-017-0319-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5701424PMC
November 2017
25 Reads

Effects of APOE haplotypes and measures of cardiovascular risk over gender-dependent cognitive and functional changes in one year in Alzheimer's disease.

Int J Neurosci 2018 May 21;128(5):472-476. Epub 2017 Nov 21.

a Department of Neurology and Neurosurgery , Escola Paulista de Medicina, Federal University of São Paulo (UNIFESP) , São Paulo , Brazil.

Background: Illiteracy, high cerebrovascular risk and copies of APOE-ϵ4 are risk factors for Alzheimer's disease dementia (AD). We aimed to investigate the impacts of gender, education, coronary heart disease (CHD) risk and creatinine clearance variations, body mass index (BMI) and APOE haplotypes over the rates of cognitive and functional decline of AD in one year.

Methods: Consecutive outpatients with late-onset AD were assessed for gender, schooling, BMI and APOE haplotypes, variations in one year of creatinine clearance and Framingham projections of the 10-year absolute CHD risk, and prospective scores of the Mini-Mental State Examination (MMSE), the Clinical Dementia Rating Sum-of-Boxes (CDR-SOB), the Index of Independence in Activities of Daily Living (ADL) and Lawton's Scale for Instrumental Activities of Daily Living (IADL). Read More

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http://dx.doi.org/10.1080/00207454.2017.1396986DOI Listing
May 2018
13 Reads

Apolipoprotein E4, Gender, Body Mass Index, Inflammation, Insulin Resistance, and Air Pollution Interactions: Recipe for Alzheimer's Disease Development in Mexico City Young Females.

J Alzheimers Dis 2017 ;58(3):613-630

Alpert Medical School of Brown University, Providence, RI, USA.

Given the epidemiological trends of increasing Alzheimer's disease (AD) and growing evidence that exposure and lifestyle factors contribute to AD risk and pathogenesis, attention should be paid to variables such as air pollution, in order to reduce rates of cognitive decline and dementia. Exposure to fine particulate matter (PM2.5) and ozone (O3) above the US EPA standards is associated with AD risk. Read More

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http://dx.doi.org/10.3233/JAD-161299DOI Listing
March 2018
109 Reads

Family history and APOE4 risk for Alzheimer's disease impact the neural correlates of episodic memory by early midlife.

Neuroimage Clin 2017 31;14:760-774. Epub 2017 Mar 31.

Brain Imaging Centre, Douglas Mental Health University Institute, Canada.

Episodic memory impairment is a consistent, pronounced deficit in pre-clinical stages of late-onset Alzheimer's disease (AD). Individuals with risk factors for AD exhibit altered brain function several decades prior to the onset of AD-related symptoms. In the current event-related fMRI study of spatial context memory we tested the hypothesis that middle-aged adults (MA; 40-58 yrs) with a family history of late onset AD (MA), or a combined + FH and apolipoprotein E ε4 allele risk factors for AD (MA), will exhibit differences in encoding and retrieval-related brain activity, compared to - FH - APOE4 MA controls. Read More

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http://dx.doi.org/10.1016/j.nicl.2017.03.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5385589PMC
April 2017
14 Reads

Increased hippocampal activation in ApoE-4 carriers and non-carriers with amnestic mild cognitive impairment.

Neuroimage Clin 2017 7;13:237-245. Epub 2016 Dec 7.

Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States.

Increased fMRI activation in the hippocampus is recognized as a signature characteristic of the amnestic mild cognitive impairment (aMCI) stage of Alzheimer's disease (AD). Previous work has localized this increased activation to the dentate gyrus/CA3 subregion of the hippocampus and showed a correlation with memory impairments in those patients. Increased hippocampal activation has also been reported in carriers of the ApoE-4 allelic variation independently of mild cognitive impairment although these findings were not localized to a hippocampal subregion. Read More

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http://dx.doi.org/10.1016/j.nicl.2016.12.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5217770PMC
November 2017
20 Reads

Genetic variants associated with risk of Alzheimer's disease contribute to cognitive change in midlife: The Atherosclerosis Risk in Communities Study.

Am J Med Genet B Neuropsychiatr Genet 2017 Apr 26;174(3):269-282. Epub 2016 Oct 26.

Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, Texas.

Alzheimer's disease (AD) is the most common form of dementia and is characterized by impairment in memory, behavioral changes, and gradual loss of autonomy. Since there is a long latent period prior to diagnosis, the aim of this study was to determine whether twenty single nucleotide polymorphisms identified in genome-wide association analyses of AD are associated with cognitive change in 8,320 white and 2,039 African-American middle-aged adults enrolled in the prospective Atherosclerosis Risk in Communities (ARIC) study. Cognition was evaluated using the Delayed Word Recall Test (DWRT; verbal memory), Digit Symbol Substitution Test (DSST; processing speed), and Word Fluency Test (WFT; executive function). Read More

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http://dx.doi.org/10.1002/ajmg.b.32509DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5935000PMC
April 2017
59 Reads

Association between Genotype and Change in Physical Function in a Population-Based Swedish Cohort of Older Individuals Followed Over Four Years.

Front Aging Neurosci 2016 4;8:225. Epub 2016 Oct 4.

Neuropsychiatric Epidemiology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg Mölndal, Sweden.

The association between decline in physical function and age-related conditions, such as reduced cognitive performance and vascular disease, may be explained by genetic influence on shared biological pathways of importance for aging. The apolipoprotein E () gene is well-known for its association with Alzheimer's disease, but has also been related to other disorders of importance for aging. The aim of this study was to investigate possible associations between allele status and physical function in a population-based longitudinal study of older individuals. Read More

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http://dx.doi.org/10.3389/fnagi.2016.00225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5047916PMC
October 2016
31 Reads

Chocolate, Air Pollution and Children's Neuroprotection: What Cognition Tools should be at Hand to Evaluate Interventions?

Front Pharmacol 2016 11;7:232. Epub 2016 Aug 11.

School of Psychology, Georgia Institute of Technology Atlanta, GA, USA.

Millions of children across the world are exposed to multiple sources of indoor and outdoor air pollutants, including high concentrations of fine particulate matter (PM2.5) and ozone (O3). The established link between exposure to PM2. Read More

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http://dx.doi.org/10.3389/fphar.2016.00232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4980563PMC
August 2016
55 Reads

Apolipoprotein E Genotype Affects Size of ApoE Complexes in Cerebrospinal Fluid.

J Neuropathol Exp Neurol 2016 Oct 11;75(10):918-924. Epub 2016 Aug 11.

From the Department of Biology (NMH, MAG); and Department of Neuroscience, Georgetown University (GWR), Washington, District of Columbia

Apolipoprotein E (apoE) is associated with lipoproteins in the cerebrospinal fluid (CSF). APOE4 increases and APOE2 decreases the risk for Alzheimer disease (AD) compared to the risk associated with APOE3 Because apoE4 is less efficient at cholesterol efflux than apoE2 or apoE3 in vitro, we hypothesized that APOE genotype may affect apoE particle size in vivo and that these size differences may be related to AD risk. We used nondenaturing gel electrophoresis to test for differences in the size of apoE complexes in human CSF samples of various APOE genotypes and created profiles of each sample to compare the patterns of apoE distribution. Read More

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http://dx.doi.org/10.1093/jnen/nlw067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996536PMC
October 2016
30 Reads

Interactive and additive influences of Gender, BMI and Apolipoprotein 4 on cognition in children chronically exposed to high concentrations of PM2.5 and ozone. APOE 4 females are at highest risk in Mexico City.

Environ Res 2016 10 2;150:411-422. Epub 2016 Jul 2.

Department of Neuroscience, Carleton University, Ottawa, Ontario, Canada.

Children's air pollution exposures are associated with systemic and brain inflammation and the early hallmarks of Alzheimer's disease (AD). The Apolipoprotein E (APOE) 4 allele is the most prevalent genetic risk for AD, with higher risk for women. We assessed whether gender, BMI, APOE and metabolic variables in healthy children with high exposures to ozone and fine particulate matter (PM2. Read More

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http://dx.doi.org/10.1016/j.envres.2016.06.026DOI Listing
October 2016
17 Reads

A novel CCM2 variant in a family with non-progressive cognitive complaints and cerebral microbleeds.

Am J Med Genet B Neuropsychiatr Genet 2017 Apr 8;174(3):220-226. Epub 2016 Jun 8.

Alzheimer Center, Department of Neurology, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, The Netherlands.

Lobar cerebral microbleeds are most often sporadic and associated with Alzheimer's disease. The aim of our study was to identify the underlying genetic defect in a family with cognitive complaints and multiple lobar microbleeds and a positive family history for early onset Alzheimer's disease. We performed exome sequencing followed by Sanger sequencing for validation purposes on genomic DNA of three siblings with cognitive complaints, reduced amyloid-beta-42 in CSF and multiple cerebral lobar microbleeds. Read More

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http://dx.doi.org/10.1002/ajmg.b.32468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363380PMC
April 2017
28 Reads

Apolipoprotein E*4 (APOE*4) Genotype Is Associated with Altered Levels of Glutamate Signaling Proteins and Synaptic Coexpression Networks in the Prefrontal Cortex in Mild to Moderate Alzheimer Disease.

Mol Cell Proteomics 2016 07 21;15(7):2252-62. Epub 2016 Apr 21.

¶Cell Biology.

It has been hypothesized that Alzheimer disease (AD) is primarily a disorder of the synapse. However, assessment of the synaptic proteome in AD subjects has been limited to a small number of proteins and often included subjects with end-stage pathology. Protein from prefrontal cortex gray matter of 59 AD subjects with mild to moderate dementia and 12 normal elderly subjects was assayed using targeted mass spectrometry to quantify 191 synaptically expressed proteins. Read More

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http://dx.doi.org/10.1074/mcp.M115.056580DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4937502PMC
July 2016
49 Reads

APOE, MAPT, and COMT and Parkinson's Disease Susceptibility and Cognitive Symptom Progression.

J Parkinsons Dis 2016 04;6(2):349-59

Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA, USA.

Background: Cognitive decline is well recognized in Parkinson's disease (PD) and a major concern for patients and caregivers. Apolipoprotein E (APOE), catechol-O-methyl transferase (COMT), and microtubule-associated protein tau (MAPT) are of interest related to their contributions to cognitive decline or dementia in PD.

Objective: Here, we investigate whether APOE, COMT, or MAPT influence the rate of cognitive decline in PD patients. Read More

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http://dx.doi.org/10.3233/JPD-150762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5927361PMC
April 2016
45 Reads
1.097 Impact Factor

Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer's disease.

Brain 2016 05 8;139(Pt 5):1551-67. Epub 2016 Mar 8.

Memory and Aging Center, University of California San Francisco, San Francisco, CA, USA Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, CA, USA.

SEE SARAZIN ET AL DOI101093/BRAIN/AWW041 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: The advent of the positron emission tomography tracer (18)F-AV1451 provides the unique opportunity to visualize the regional distribution of tau pathology in the living human brain. In this study, we tested the hypothesis that tau pathology is closely linked to symptomatology and patterns of glucose hypometabolism in Alzheimer's disease, in contrast to the more diffuse distribution of amyloid-β pathology. We included 20 patients meeting criteria for probable Alzheimer's disease dementia or mild cognitive impairment due to Alzheimer's disease, presenting with a variety of clinical phenotypes, and 15 amyloid-β-negative cognitively normal individuals, who underwent (18)F-AV1451 (tau), (11)C-PiB (amyloid-β) and (18)F-FDG (glucose metabolism) positron emission tomography, apolipoprotein E (APOE) genotyping and neuropsychological testing. Read More

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http://dx.doi.org/10.1093/brain/aww027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5006248PMC
May 2016
121 Reads
9.196 Impact Factor

Apolipoprotein E genotype is not associated with cognitive impairment in older adults with bipolar disorder.

Bipolar Disord 2016 Feb 15;18(1):71-7. Epub 2016 Feb 15.

Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo (USP), São Paulo, SP, Brazil.

Objectives: Cognitive decline is part of the long-term outcome for many individuals with bipolar disorder (BD). The ε4 allele (APOE*4) of apolipoprotein E (APOE) is a well-established risk factor for dementia in Alzheimer's disease (AD). However, its contribution to the risk of cognitive deterioration in BD has not yet been determined. Read More

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http://dx.doi.org/10.1111/bdi.12367DOI Listing
February 2016
18 Reads

Cerebral microbleeds as a biomarker in Alzheimer's disease? A review in the field.

Biomark Med 2016 7;10(1):9-18. Epub 2015 Dec 7.

Department of Neurobiology, Care Sciences & Society, Karolinska Institutet, Stockholm, Sweden. Division of Clinical Geriatrics, Karolinska University Hospital, Stockholm, Sweden.

Cerebral microbleeds (CMBs) are a marker of small vessel disease, increasingly recognized as being of importance in the Alzheimer's disease (AD) process. CMBs influence in AD, and its longitudinal impact on disease progression is however still unknown. CMBs show several associations with AD across studies, are associated with decreased cerebrospinal fluid amyloid levels and are related with the ApoE ϵ4 allele, as well as other imaging manifestations typical for small vessel disease. Read More

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http://dx.doi.org/10.2217/bmm.15.101DOI Listing
September 2016
67 Reads

Cognitive and Psychiatric Disturbances in Parkinsonian Syndromes.

Neurol Clin 2016 Feb;34(1):235-46

Department of Neurology, Louisiana State University Health Sciences Center - Shreveport, 1501 King's Highway, Shreveport, LA 71103, USA.

Parkinsonian syndromes share clinical signs including akinesia/bradykinesia and rigidity, which are consequences of pathology involving dopaminergic substantia nigra neurons. Yet cognitive and psychiatric disturbances are common, even early in the course of disease. Executive dysfunction is often measurable in newly diagnosed Parkinson's disease. Read More

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http://dx.doi.org/10.1016/j.ncl.2015.08.010DOI Listing
February 2016
40 Reads

Apolipoprotein E ϵ4 is positively related to spatial performance but unrelated to hippocampal volume in healthy young adults.

Behav Brain Res 2016 Feb 12;299:11-8. Epub 2015 Nov 12.

Department of Psychology, Uppsala University, Uppsala, Sweden.

The apolipoprotein E (APOE) ϵ4 allele is known to be a major genetic risk factor for Alzheimer's disease (AD). It has been linked to especially episodic memory decline and hippocampal atrophy in both healthy and demented elderly populations. In young adults, ϵ4 carriers have shown better performance in episodic memory compared to non-carriers. Read More

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http://dx.doi.org/10.1016/j.bbr.2015.11.006DOI Listing
February 2016
14 Reads

Murine versus human apolipoprotein E4: differential facilitation of and co-localization in cerebral amyloid angiopathy and amyloid plaques in APP transgenic mouse models.

Acta Neuropathol Commun 2015 Nov 10;3:70. Epub 2015 Nov 10.

Department of Neurology, Hope Center for Neurological Disorders, Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, 63110, USA.

Introduction: Amyloid β (Aβ) accumulates in the extracellular space as diffuse and neuritic plaques in Alzheimer's disease (AD). Aβ also deposits on the walls of arterioles as cerebral amyloid angiopathy (CAA) in most cases of AD and sometimes independently of AD. Apolipoprotein E (apoE) ɛ4 is associated with increases in both Aβ plaques and CAA in humans. Read More

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http://dx.doi.org/10.1186/s40478-015-0250-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4641345PMC
November 2015
68 Reads
1 Citation

SPECTRAL GRAPH THEORY AND GRAPH ENERGY METRICS SHOW EVIDENCE FOR THE ALZHEIMER'S DISEASE DISCONNECTION SYNDROME IN -4 RISK GENE CARRIERS.

Proc IEEE Int Symp Biomed Imaging 2015 Apr;2015:458-461

Imaging Genetics Center, Institute for Neuroimaging & Informatics, University of Southern California.

Our understanding of network breakdown in Alzheimer's disease (AD) is likely to be enhanced through advanced mathematical descriptors. Here, we applied spectral graph theory to provide novel metrics of structural connectivity based on 3-Tesla diffusion weighted images in 42 AD patients and 50 healthy controls. We reconstructed connectivity networks using whole-brain tractography and examined, for the first time here, cortical disconnection based on the graph energy and spectrum. Read More

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http://dx.doi.org/10.1109/ISBI.2015.7163910DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4578320PMC
April 2015
38 Reads

Examining the association between Apolipoprotein E (APOE) and self-reported sleep disturbances in non-demented older adults.

Neurosci Lett 2015 Oct 24;606:72-6. Epub 2015 Aug 24.

The Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA.

We aimed to examine the association between Apolipoprotein E (APOE) and sleep disturbances. This is a cross-sectional study, from the Washington Heights-Inwood Community Aging Project (WHICAP). A total of 1944 non-demented older adults took part in the study. Read More

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http://dx.doi.org/10.1016/j.neulet.2015.08.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4598304PMC
October 2015
39 Reads

Prion Disease Induces Alzheimer Disease-Like Neuropathologic Changes.

J Neuropathol Exp Neurol 2015 Sep;74(9):873-88

From the Department of Pathology (Neuropathology) (TT, KB, HS, AG, AO, BD, SJD), Department of Neurology (MG), Memory and Aging Center (MG), and Institute for Neurodegenerative Diseases (SJD), University of California San Francisco, San Francisco, California.

We examined the brains of 266 patients with prion disease (PrionD) and found that 46 patients (17%) had Alzheimer disease (AD)-like changes. To explore potential mechanistic links between PrionD and AD, we exposed human brain aggregates (BrnAggs) to a brain homogenate from a patient with sporadic Creutzfeldt-Jakob disease and found that neurons in human BrnAggs produced many β-amyloid (Aβ; Aβ42) inclusions, whereas uninfected control-exposed human BrnAggs did not. Western blot analysis of 20 pooled Creutzfeldt-Jakob disease-infected BrnAggs verified Aβ42 levels higher than those in controls. Read More

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http://dx.doi.org/10.1097/NEN.0000000000000228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5094352PMC
September 2015
72 Reads