Genetic Factors in Early- and Late-Onset Alzheimer’s Disease

ABSTRACTThe high genetic heritability of Alzheimer’s disease has contributed to the multi-directional and large-scale genomic studies to discover genetic factors, and so far many massive studies have been reported. However, the majority of genetic factors have been identified through European races, and relatively few studies using East Asians to discover genetic factors. In this study, East Asian specific loci is first reported through GWAS using GARD cohorts, which have been intensively recruited and managed by a single institution. ApoE-stratified GWAS with the AD cases and matched controls (n=2,291) in the Korean cohort and validation analysis using a Japanese sample (n=1,956) replicated six previously reported loci (genes) including ApoE and suggested two novel susceptible loci in LRIG1 and CACNA1A gene. This study demonstrates that discovery of AD-associated variants can be accomplished in ethnic groups of a more homogeneous genetic background using samples comprising fewer subjects.

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A Global Review on Alzheimer’s Disease

International Journal of Pharmaceutical Sciences Review and Research ◽

10.47583/ijpsrr.2021.v68i01.017 ◽

2021 ◽

Vol 68 (1) ◽

Author(s):

Natarajan. P ◽

Mumthaj. P ◽

Vijay. J ◽

Gokul. V

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cholinesterase Inhibitors ◽

Genetic Factors ◽

Environmental Changes ◽

Late Onset ◽

Memory Loss ◽

Review Article ◽

Acetyl Cholinesterase ◽

Alois Alzheimer

Alzheimer’s disease (AD) is an inevitable neurological disorder in which the death of brain cells causes memory loss and cognitive decline and ultimate dementia. It’s the foremost common cause of dementia in people of 65 years and older. It was first described by a neurologist Alois Alzheimer in 1906. This review article gives an account on the various symptoms from pre-dementia to severe Alzheimer’s dementia. The Alzheimer’s disease is caused by the pathogenesis by accumulation of toxic amyloid-? plaques (A?) and Hyper phosphorylated tau (p-tau). The greatest risk factors for late onset Alzheimer’s are age, genetics, family history and non-genetic factors (heart health, life style modifications, and environmental changes). The diagnosis of AD advances in genetics, the event of biomarkers of neuro degeneration and neuroimaging discovery utilizes the method to detect AD. The medication use to treat AD is acetyl cholinesterase inhibitors and N-methyl D aspartate antagonists and various drugs are under clinical trials.

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Is very late onset Alzheimer's disease influenced by genetic factors?

Neurobiology of Aging ◽

10.1016/s0197-4580(00)82111-9 ◽

2000 ◽

Vol 21 ◽

pp. 172

Author(s):

Jeremy M. Silverman ◽

Christopher J. Smith ◽

Deborah B. Marin ◽

Ana M. Bisono ◽

Richard C. Mohs ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Genetic Factors ◽

Late Onset

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Genetic factors associated with the predisposition to late onset Alzheimer's disease

Gene ◽

10.1016/j.gene.2019.05.030 ◽

2019 ◽

Vol 707 ◽

pp. 212-215 ◽

Cited By ~ 6

Author(s):

Asude Durmaz ◽

Emre Kumral ◽

Burak Durmaz ◽

Huseyin Onay ◽

Gulcin Itirli Aslan ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Genetic Factors ◽

Late Onset ◽

Factors Associated

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Genetic Factors Affecting Late-Onset Alzheimer’s Disease Susceptibility

NeuroMolecular Medicine ◽

10.1007/s12017-015-8376-4 ◽

2015 ◽

Vol 18 (1) ◽

pp. 37-49 ◽

Cited By ~ 17

Author(s):

Maryam Rezazadeh ◽

Aziz Khorrami ◽

Tarlan Yeghaneh ◽

Mahnaz Talebi ◽

Seyed Jalal Kiani ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Genetic Factors ◽

Disease Susceptibility ◽

Late Onset ◽

Factors Affecting

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

PsycEXTRA Dataset ◽

10.1037/e334202004-004 ◽

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

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

Current Protein and Peptide Science ◽

10.2174/1389203721666200921152246 ◽

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.

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

Current Gene Therapy ◽

10.2174/1566523220666201123112822 ◽

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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Alzheimer’s Disease and Retinal Degeneration: A Glimpse at Essential Trace Metals in Ocular Fluids and Tissues

Current Alzheimer Research ◽

10.2174/1567205016666191023114015 ◽

2020 ◽

Vol 16 (12) ◽

pp. 1073-1083 ◽

Cited By ~ 3

Author(s):

Alessandra Micera ◽

Luca Bruno ◽

Andrea Cacciamani ◽

Mauro Rongioletti ◽

Rosanna Squitti

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Trace Metals ◽

Late Onset ◽

Current Knowledge ◽

Pathological Condition ◽

Retinal Disease ◽

Cellular Aging ◽

Research Strategies ◽

Aged People

Background: Life expectancy is increasing all over the world, although neurodegenerative disorders might drastically affect the individual activity of aged people. Of those, Alzheimer’s Disease (AD) is one of the most social-cost age-linked diseases of industrialized countries. To date, retinal diseases seem to be more common in the developing world and characterize principally aged people. Agerelated Macular Degeneration (AMD) is a late-onset, neurodegenerative retinal disease that shares several clinical and pathological features with AD, including stress stimuli such as oxidative stress, inflammation and amyloid formations. Method: In both diseases, the detrimental intra/extra-cellular deposits have many similarities. Aging, hypercholesterolemia, hypertension, obesity, arteriosclerosis and smoking are risk factors to develop both diseases. Cellular aging routes have similar organelle and signaling patterns in retina and brain. The possibility to find out new research strategies represent a step forward to disclose potential treatment for both of them. Essential trace metals play critical roles in both physiological and pathological condition of retina, optic nerve and brain, by influencing metabolic processes chiefly upon complex multifactorial pathogenesis. Conclusion: Hence, this review addresses current knowledge about some up-to-date investigated essential trace metals associated with AD and AMD. Changes in the levels of systemic and ocular fluid essential metals might reflect the early stages of AMD, possibly disclosing neurodegeneration pathways shared with AD, which might open to potential early detection.

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