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

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 Genetic and epigenetic study of an Alzheimer’s disease family with monozygotic triplets

Brain ◽  
2019 ◽  
Vol 142 (11) ◽  
pp. 3375-3381 ◽  
Author(s):  
Ming Zhang ◽  
Allison A Dilliott ◽  
Roaa Khallaf ◽  
John F Robinson ◽  
Robert A Hegele ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Onset ◽  
Late Onset ◽  
Accelerated Ageing ◽  
Disease Phenotypes ◽  
Apoe Ε4 ◽  
Ε4 Allele ◽  
Disease Family

Zhang, Dilliott et al. examine a unique family with early- and late-onset Alzheimer’s disease phenotypes, as well as disease-discordant monozygotic triplets. The triplets and the patient with early-onset disease are carriers of the APOE ε4-allele plus rare substitutions in other genes. Epigenetic analyses suggest accelerated ageing in the early-onset patient.

scholarly journals Assessment and familial aggregation of psychosis in Alzheimer's disease from the National Institute on Aging Late Onset Alzheimer's Disease Family Study

Brain ◽  
2010 ◽  
Vol 133 (4) ◽  
pp. 1155-1162 ◽  
Author(s):  
R. A. Sweet ◽  
D. A. Bennett ◽  
N. R. Graff-Radford ◽  
R. Mayeux ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Family Study ◽  
Late Onset ◽  
Familial Aggregation ◽  
Disease Family

scholarly journals Heritability of Different Forms of Memory in the Late Onset Alzheimer's Disease Family Study

2011 ◽  
Vol 23 (2) ◽  
pp. 249-255 ◽  
Author(s):  
Robert S. Wilson ◽  
Sandra Barral ◽  
Joseph H. Lee ◽  
Sue E. Leurgans ◽  
Tatiana M. Foroud ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Family Study ◽  
Late Onset ◽  
Disease Family

Familial Patterns of Risk in Very Late-Onset Alzheimer's Disease

2003 ◽  
Author(s):  
J. M. Silverman ◽  
C. J. Smith ◽  
D. B. Marin ◽  
R. C. Mohs ◽  
C. B. Propper
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Late Onset ◽  
Familial Patterns

Exploring the Role of Aggregated Proteomes in the Pathogenesis of Alzheimer’s Disease

2020 ◽  
Vol 21 (12) ◽  
pp. 1164-1173
Author(s):  
Siju Ellickal Narayanan ◽  
Nikhila Sekhar ◽  
Rajalakshmi Ganesan Rajamma ◽  
Akash Marathakam ◽  
Abdullah Al Mamun ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Precursor Protein ◽  
Early Onset ◽  
Late Onset ◽  
Precursor Protein ◽  
Brain Disorder ◽  
Amyloid Aβ ◽  
T Tau

: Alzheimer’s disease (AD) is a progressive brain disorder and one of the most common causes of dementia and death. AD can be of two types; early-onset and late-onset, where late-onset AD occurs sporadically while early-onset AD results from a mutation in any of the three genes that include amyloid precursor protein (APP), presenilin 1 (PSEN 1) and presenilin 2 (PSEN 2). Biologically, AD is defined by the presence of the distinct neuropathological profile that consists of the extracellular β-amyloid (Aβ) deposition in the form of diffuse neuritic plaques, intraneuronal neurofibrillary tangles (NFTs) and neuropil threads; in dystrophic neuritis, consisting of aggregated hyperphosphorylated tau protein. Elevated levels of (Aβ), total tau (t-tau) and phosphorylated tau (ptau) in cerebrospinal fluid (CSF) have become an important biomarker for the identification of this neurodegenerative disease. The aggregation of Aβ peptide derived from amyloid precursor protein initiates a series of events that involve inflammation, tau hyperphosphorylation and its deposition, in addition to synaptic dysfunction and neurodegeneration, ultimately resulting in dementia. The current review focuses on the role of proteomes in the pathogenesis of AD.

Molecular Genetics of Early- and Late-Onset Alzheimer’s Disease

2020 ◽  
Vol 20 ◽  
Author(s):  
Md. Sahab Uddin ◽  
Sharifa Hasana ◽  
Md. Farhad Hossain ◽  
Md. Siddiqul Islam ◽  
Tapan Behl ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Massively Parallel Sequencing ◽  
Late Onset ◽  
Current Knowledge ◽  
The Elderly ◽  
Apoe Ε4 ◽  
Sequencing Technologies ◽  
Genetic Components ◽  
Ε4 Allele

: Alzheimer’s disease (AD) is the most common form of dementia in the elderly and this complex disorder is associated with environmental as well as genetic components. Early-onset AD (EOAD) and late-onset AD (LOAD, more common) are major identified types of AD. The genetics of EOAD is extensively understood with three genes variants such as APP, PSEN1, and PSEN2 leading to disease. On the other hand, some common alleles including APOE are effectively associated with LOAD identified but the genetics of LOAD is not clear to date. It has been accounted that about 5% to 10% of EOAD patients can be explained through mutations in the three familiar genes of EOAD. The APOE ε4 allele augmented the severity of EOAD risk in carriers, and APOE ε4 allele was considered as a hallmark of EOAD. A great number of EOAD patients, who are not genetically explained, indicate that it is not possible to identify disease- triggering genes yet. Although several genes have been identified through using the technology of next-generation sequencing in EOAD families including SORL1, TYROBP, and NOTCH3. A number of TYROBP variants were identified through exome sequencing in EOAD patients and these TYROBP variants may increase the pathogenesis of EOAD. The existence of ε4 allele is responsible for increasing the severity of EOAD. However, several ε4 allele carriers live into their 90s that propose the presence of other LOAD genetic as well as environmental risk factors that are not identified yet. It is urgent to find out missing genetics of EOAD and LOAD etiology to discover new potential genetics facets which will assist to understand the pathological mechanism of AD. These investigations should contribute to developing a new therapeutic candidate for alleviating, reversing and preventing AD. This article based on current knowledge represents the overview of the susceptible genes of EOAD, and LOAD. Next, we represent the probable molecular mechanism which might elucidate the genetic etiology of AD and highlight the role of massively parallel sequencing technologies for novel gene discoveries.

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