Insight into the genetic etiology of Alzheimer's disease: A comprehensive review of the role of rare variants

Background: The complication of Alzheimer’s disease (AD) has made the development of its therapeutic a challenging task. Even after decades of research, we have achieved no more than a few years of symptomatic relief. The inability to diagnose the disease early is the foremost hurdle behind its treatment. Several studies have aimed to identify potential biomarkers that can be detected in body fluids (CSF, blood, urine, etc) or assessed by neuroimaging (i.e., PET and MRI). However, the clinical implementation of these biomarkers is incomplete as they cannot be validated. Method: To overcome the limitation, the use of artificial intelligence along with technical tools has been extensively investigated for AD diagnosis. For developing a promising artificial intelligence strategy that can diagnose AD early, it is critical to supervise neuropsychological outcomes and imaging-based readouts with a proper clinical review. Conclusion: Profound knowledge, a large data pool, and detailed investigations are required for the successful implementation of this tool. This review will enlighten various aspects of early diagnosis of AD using artificial intelligence.

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Redox proteomics studies ofin vivo amyloid beta-peptide animal models of Alzheimer's disease: Insight into the role of oxidative stress

PROTEOMICS - CLINICAL APPLICATIONS ◽

10.1002/prca.200780024 ◽

2008 ◽

Vol 2 (5) ◽

pp. 685-696 ◽

Cited By ~ 11

Author(s):

Rukhsana Sultana ◽

D. Allan Butterfield

Keyword(s):

Oxidative Stress ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Animal Models ◽

Amyloid Beta ◽

Amyloid Beta Peptide ◽

Redox Proteomics ◽

Beta Peptide ◽

Insight Into

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P1-046: ROLE OF PLD3 RARE VARIANTS IN EUROPEAN SPORADIC ALZHEIMER'S DISEASE PATIENTS

Alzheimer s & Dementia ◽

10.1016/j.jalz.2014.05.281 ◽

2014 ◽

Vol 10 ◽

pp. P319-P320

Author(s):

Alfredo Ramirez ◽

Stefanie Heilmann ◽

Dmitriy Drichel ◽

Isabel Hernandez ◽

Alberto Lleó ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Rare Variants ◽

Sporadic Alzheimer’S Disease

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Investigation of the role of matrix metalloproteinases in the genetic etiology of Alzheimer's disease

Neurobiology of Aging ◽

10.1016/j.neurobiolaging.2021.03.011 ◽

2021 ◽

Author(s):

Julie Hoogmartens ◽

Elisabeth Hens ◽

Sebastiaan Engelborghs ◽

Peter Paul De Deyn ◽

Julie van der Zee ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Matrix Metalloproteinases ◽

Genetic Etiology

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Long Non-coding RNA: Insight Into Mechanisms of Alzheimer's Disease

Frontiers in Molecular Neuroscience ◽

10.3389/fnmol.2021.821002 ◽

2022 ◽

Vol 14 ◽

Author(s):

Zhen Lan ◽

Yanting Chen ◽

Jiali Jin ◽

Yun Xu ◽

Xiaolei Zhu

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Neurodegenerative Disorder ◽

Vital Role ◽

Biological Functions ◽

Non Coding Rna ◽

Non Coding Rnas ◽

Long Non Coding Rna ◽

Insight Into

Alzheimer's disease (AD), a heterogeneous neurodegenerative disorder, is the most common cause of dementia accounting for an estimated 60–80% of cases. The pathogenesis of AD remains unclear, and no curative treatment is available so far. Increasing evidence has revealed a vital role of non-coding RNAs (ncRNAs), especially long non-coding RNAs (lncRNAs), in AD. LncRNAs contribute to the pathogenesis of AD via modulating amyloid production, Tau hyperphosphorylation, mitochondrial dysfunction, oxidative stress, synaptic impairment and neuroinflammation. This review describes the biological functions and mechanisms of lncRNAs in AD, indicating that lncRNAs may provide potential therapeutic targets for the diagnosis and treatment of AD.

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Delta-secretase cleavage of Tau mediates its pathology and propagation in Alzheimer’s disease

Experimental & Molecular Medicine ◽

10.1038/s12276-020-00494-7 ◽

2020 ◽

Vol 52 (8) ◽

pp. 1275-1287

Author(s):

Seong Su Kang ◽

Eun Hee Ahn ◽

Keqiang Ye

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Therapeutic Strategy ◽

Senile Plaques ◽

Tau Pathology ◽

Disease Modifying ◽

Tau Aggregation ◽

The Brain ◽

Insight Into

Abstract Alzheimer’s disease (AD) is a progressive neurodegenerative disease with age as a major risk factor. AD is the most common dementia with abnormal structures, including extracellular senile plaques and intraneuronal neurofibrillary tangles, as key neuropathologic hallmarks. The early feature of AD pathology is degeneration of the locus coeruleus (LC), which is the main source of norepinephrine (NE) supplying various cortical and subcortical areas that are affected in AD. The spread of Tau deposits is first initiated in the LC and is transported in a stepwise manner from the entorhinal cortex to the hippocampus and then to associative regions of the neocortex as the disease progresses. Most recently, we reported that the NE metabolite DOPEGAL activates delta-secretase (AEP, asparagine endopeptidase) and triggers pathological Tau aggregation in the LC, providing molecular insight into why LC neurons are selectively vulnerable to developing early Tau pathology and degenerating later in the disease and how δ-secretase mediates the spread of Tau pathology to the rest of the brain. This review summarizes our current understanding of the crucial role of δ-secretase in driving and spreading AD pathologies by cleaving multiple critical players, including APP and Tau, supporting that blockade of δ-secretase may provide an innovative disease-modifying therapeutic strategy for treating AD.

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