scholarly journals The National Institute on Aging Late Onset Alzheimer's Disease Family Based Study: A Critical Component of the International Effort to Understand Alzheimer's Disease

2021 ◽  
Author(s):  
Dolly Reyes-Dumeyer ◽  
Kelley Faber ◽  
Badri N. Vardarajan ◽  
Alison Goate ◽  
Alan Renton ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Late Onset ◽  
Age At Onset ◽  
Apoe Genotype ◽  
Alzheimers Disease ◽  
Genetic Etiology ◽  
Wide Range ◽  
Family Based ◽  
Disease Family

INTRODUCTION: The National Institute on Aging Late-Onset Alzheimers Disease Family Based Study (NIA-LOAD FBS) was established to study the genetic etiology of Alzheimers disease (AD). METHODS: Recruitment focused on families with two living affected siblings and a third first degree relative similar in age with or without dementia. Uniform assessments were completed, DNA was obtained as was neuropathology, when possible. APOE genotypes, genome-wide SNP arrays and sequencing was completed in the majority of families. RESULTS: A wide range in the age-at-onset in many large families was related to APOE genotype, but not in all. Variants typically associated with early-onset AD and frontotemporal dementia were also found. DISCUSSION: The NIA-LOAD FBS is the largest collection of familial AD worldwide, and data or samples have been included in 126 publications addressing the genetic etiology of AD. Genetic heterogeneity and variability in the age-at-onset provides opportunities to investigate the complexity of familial AD.

scholarly journals The National Institute on Aging Late‐Onset Alzheimer's Disease Family Based Study: A resource for genetic discovery

2022 ◽  
Author(s):  
Dolly Reyes‐Dumeyer ◽  
Kelley Faber ◽  
Badri Vardarajan ◽  
Alison Goate ◽  
Alan Renton ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Late Onset ◽  
Family Based ◽  
Genetic Discovery ◽  
Disease Family

Most rapid cognitive decline in APOE ε4 negative Alzheimer's disease with early onset

2009 ◽  
Vol 39 (11) ◽  
pp. 1907-1911 ◽  
Author(s):  
A. E. van der Vlies ◽  
E. L. G. E. Koedam ◽  
Y. A. L. Pijnenburg ◽  
J. W. R. Twisk ◽  
P. Scheltens ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Early Onset ◽  
Late Onset ◽  
Age At Onset ◽  
Apoe Genotype ◽  
Apoe Ε4 ◽  
Rapid Cognitive Decline ◽  
State Examination

BackgroundWe aimed to compare the rate of cognitive decline in patients with early and late onset Alzheimer's disease (AD) and to investigate the potentially modifying influence of the apolipoprotein E (APOE) genotype.MethodWe included 99 patients with early onset AD (age ⩽65 years) and 192 patients with late onset AD (age >65 years) who had at least two scores on the Mini-Mental State Examination (MMSE) (range 2–14) obtained at least 1 year apart. Linear mixed models were performed to investigate the rate of cognitive decline dependent on age at onset (AAO) and APOE genotype.ResultsThe mean (s.d.) age for patients with early onset AD was 57.7 (4.5) years, and 74.5 (5.1) years for patients with late onset AD. AAO was not associated with baseline MMSE [β (s.e.)=0.8 (0.5), p=0.14]. However, patients with early onset showed a faster decline on the MMSE [β (s.e.)=2.4 (0.1) points/year] than those with late onset [β (s.e.)=1.7 (0.1) points/year, p=0.00]. After stratification according to APOE genotype, APOE ε4 non-carriers with early onset showed faster cognitive decline than non-carriers with late onset [2.4 (0.3) v. 1.3 (0.3) points/year, p=0.01]. In APOE ε4 carriers, no difference in rate of cognitive decline was found between patients with early and late onset [β (s.e.)=0.2 (0.2), p=0.47].ConclusionPatients with early onset AD show more rapid cognitive decline than patients with late onset, suggesting that early onset AD follows a more aggressive course. Furthermore, this effect seems to be most prominent in patients with early onset who do not carry the genetic APOE ε4 risk factor for AD.

Race-Related Association between APOE Genotype and Alzheimer’s Disease: A Systematic Review and Meta-Analysis

2021 ◽  
pp. 1-10
Author(s):  
Wei Qin ◽  
Wenwen Li ◽  
Qi Wang ◽  
Min Gong ◽  
Tingting Li ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Black People ◽  
Late Onset ◽  
Meta Analysis ◽  
Group Analysis ◽  
Apoe Genotype ◽  
Cochrane Library ◽  
Data Sets ◽  
Apoe Genotypes

Background: The global race-dependent association of Alzheimer’s disease (AD) and apolipoprotein E (APOE) genotype is not well understood. Transethnic analysis of APOE could clarify the role of genetics in AD risk across populations. Objective: This study aims to determine how race and APOE genotype affect the risks for AD. Methods: We performed a systematic search of PubMed, Embase, Web of Science, and the Cochrane Library since 1993 to Aug 25, 2020. A total of 10,395 reports were identified, and 133 were eligible for analysis with data on 77,402 participants. Studies contained AD clinical diagnostic and APOE genotype data. Homogeneous data sets were pooled in case-control analyses. Odds ratios and 95% confidence intervals for developing AD were calculated for populations of different races and APOE genotypes. Results: The proportion of APOE genotypes and alleles differed between populations of different races. Results showed that APOE ɛ4 was a risk factor for AD, whereas APOE ɛ2 protected against it. The effects of APOE ɛ4 and ɛ2 on AD risk were distinct in various races, they were substantially attenuated among Black people. Sub-group analysis found a higher frequency of APOE ɛ4/ɛ4 and lower frequency of APOE ɛ3/ɛ3 among early-onset AD than late-onset AD in a combined group and different races. Conclusion: Our meta-analysis suggests that the association of APOE genotypes and AD differ between races. These results enhance our understanding of APOE-related risk for AD across race backgrounds and provide new insights into precision medicine for AD.

scholarly journals Late Onset Alzheimer Dementia in Patients with Genotype E3/E4: A Case Report

2021 ◽  
Vol 9 (C) ◽  
pp. 5-9
Author(s):  
Anak Agung Ayu Putri Laksmidewi ◽  
Chiquita Putri Vania Rau
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Case Report ◽  
Mini Mental State Examination ◽  
Late Onset ◽  
Apoe Genotype ◽  
Time Orientation ◽  
Alzheimer Dementia ◽  
The Family ◽  
State Examination

BACKGROUND: Dementia is one of the leading causes of disability and dependence in elderly worldwide. Epidemiological statistics indicate that data show that at about 60–80%, Alzheimer’s is the most common type of dementia. Alzheimer’s is also the third-most prominent cause of death in elderly. CASE REPORT: A 72-years-old male patient, complained by the family often forgets about things that have just been done for 3 years ago. According to the family, patient also often discussing the same things repeatedly. Patients tend not to have the initiative to start his daily activities. The family admitted that patient also became often angry and felt suspicious for the last 2 years. From the mini mental state examination showed disturbances in time orientation and recall; from Montreal Cognitive Assessment Ina found disturbances in visuospatial, fluency, abstraction, delayed memory, and time orientation; accompanied by activities of daily living (ADL) and instrumental ADL disorders. Patient also performed a molecular examination of the apolipoprotein E (APOE) genotype and the genotype E3/E4 was detected. CONCLUSION: The function of the APOE gene, in particular APOE4, is the most emphasized genetic relationship in late onset Alzheimer’s disease. It is proposed that blocking the action of APOE4 can delay or stop Alzheimer’s disease progression.

scholarly journals Shared genetic etiology underlying late‐onset Alzheimer's disease and posttraumatic stress syndrome

2020 ◽  
Vol 16 (9) ◽  
pp. 1280-1292
Author(s):  
Michael W. Lutz ◽  
Sheng Luo ◽  
Douglas E. Williamson ◽  
Ornit Chiba‐Falek
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Posttraumatic Stress ◽  
Late Onset ◽  
Posttraumatic Stress Syndrome ◽  
Genetic Etiology ◽  
Stress Syndrome ◽  
Shared Genetic

O2-06-06: SNPS in MAPT are associated with cerebrospinal fluid Tau levels, MAPT mRNA levels, and age at onset of late-onset Alzheimer's disease

2008 ◽  
Vol 4 ◽  
pp. T145-T145
Author(s):  
John S.K. Kauwe ◽  
Carlos Cruchaga ◽  
Kevin Mayo ◽  
Chiara Fenoglio ◽  
Sarah Bertelsen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Late Onset ◽  
Age At Onset ◽  
Mrna Levels

scholarly journals Family-based association analysis of NAV2 gene with the risk and age at onset of Alzheimer's disease

2017 ◽  
Vol 310 ◽  
pp. 60-65 ◽  
Author(s):  
Ke-Sheng Wang ◽  
Ying Liu ◽  
Chun Xu ◽  
Xuefeng Liu ◽  
Xingguang Luo
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Association Analysis ◽  
Age At Onset ◽  
Family Based

scholarly journals Network propagation of rare variants in Alzheimer’s disease reveals tissue-specific hub genes and communities

2021 ◽  
Vol 17 (1) ◽  
pp. e1008517
Author(s):  
Marzia Antonella Scelsi ◽  
Valerio Napolioni ◽  
Michael D. Greicius ◽  
Andre Altmann ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Rare Variants ◽  
Late Onset ◽  
Integrative Approach ◽  
Specific Gene ◽  
Tissue Specific ◽  
Association Testing ◽  
Wide Range ◽  
Network Propagation

State-of-the-art rare variant association testing methods aggregate the contribution of rare variants in biologically relevant genomic regions to boost statistical power. However, testing single genes separately does not consider the complex interaction landscape of genes, nor the downstream effects of non-synonymous variants on protein structure and function. Here we present the NETwork Propagation-based Assessment of Genetic Events (NETPAGE), an integrative approach aimed at investigating the biological pathways through which rare variation results in complex disease phenotypes. We applied NETPAGE to sporadic, late-onset Alzheimer’s disease (AD), using whole-genome sequencing from the AD Neuroimaging Initiative (ADNI) cohort, as well as whole-exome sequencing from the AD Sequencing Project (ADSP). NETPAGE is based on network propagation, a framework that models information flow on a graph and simulates the percolation of genetic variation through tissue-specific gene interaction networks. The result of network propagation is a set of smoothed gene scores that can be tested for association with disease status through sparse regression. The application of NETPAGE to AD enabled the identification of a set of connected genes whose smoothed variation profile was robustly associated to case-control status, based on gene interactions in the hippocampus. Additionally, smoothed scores significantly correlated with risk of conversion to AD in Mild Cognitive Impairment (MCI) subjects. Lastly, we investigated tissue-specific transcriptional dysregulation of the core genes in two independent RNA-seq datasets, as well as significant enrichments in terms of gene sets with known connections to AD. We present a framework that enables enhanced genetic association testing for a wide range of traits, diseases, and sample sizes.

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