Gene mutations associated with early onset familial Alzheimer’s disease in China: An overview and current status

Qin, Qi; Yin, Yun; Wang, Yan; Lu, Yuanyuan; Tang, Yi; Jia, Jianping

doi:10.1002/mgg3.1443

Cited by 17 publications

(8 citation statements)

References 116 publications

(161 reference statements)

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“…The study also investigated the causes of low CCT2 expression and observed that gene mutations, DNA methylation, and miRNA may cause changes in gene expression, causing AD ( Qin et al, 2020 ; De Jager et al, 2014 ; Akhter and Bekris, 2019 ). Thus, we aimed to explore the miRNA interacting with hub genes, most of which had the opposite expression profile of their target genes in AD.…”

Section: Discussionmentioning

confidence: 99%

Multi-omics analysis revealed the role of CCT2 in the induction of autophagy in Alzheimer’s disease

Feng

Quan

et al. 2023

Front. Genet.

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Chaperonin containing TCP1 subunit 2 (CCT2) is essential in various neurodegenerative diseases, albeit its role in the pathogenesis of Alzheimer’s disease (AD) remains elusive. This study aimed to evaluate the role of CCT2 in Alzheimer’s disease. First, bioinformatics database analysis revealed that CCT2 was significantly downregulated in patients with Alzheimer’s disease and associated with autophagic clearance of β-amyloid. The 789 differentially expressed genes overlapped in AD-group and CCT2-low/high group, and the CCT2-high-associated genes screened by Pearson coefficients were enriched in protein folding, autophagy, and messenger RNA stability regulation pathways. These results suggest that CCT2 is significantly and positively associated with multiple pathways linked to autophagy and negatively associated with neuronal death. The logistic prediction model with 13 key genes, such as CCT2, screened in this study better predicts Alzheimer’s disease occurrence (AUC = 0.9671) and is a favorable candidate for predicting potential biological targets of Alzheimer’s disease. Additionally, this study predicts reciprocal micro RNAs and small molecule drugs for hub genes. Our findings suggest that low CCT2 expression may be responsible for the autophagy suppression in Alzheimer’s disease, providing an accurate explanation for its pathogenesis and new targets and small molecule inhibitors for its treatment.

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Section: Discussionmentioning

confidence: 99%

Multi-omics analysis revealed the role of CCT2 in the induction of autophagy in Alzheimer’s disease

Feng

Quan

et al. 2023

Front. Genet.

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“…The following best characterized gene variants are associated with increased amyloid load (Raux, 2005;Bekris et al, 2010;Xiao et al, 2021). Variants in the Presenilin-1 (PSEN1) gene, Amyloid Precursor Protein (APP) gene, and Presenilin-2 (PSEN2) gene cause early-onset Mendez, 2019;Qin et al, 2020;Xiao et al, 2021). PSEN1 encodes Presenilin-1, the proteolytic subunit of γ-secretase, which is known to process APP (medlineplus.gov, 2021).…”

Section: Ad Genetic Risk Factorsmentioning

confidence: 99%

Emerging Alzheimer’s disease therapeutics: promising insights from lipid metabolism and microglia-focused interventions

Tobeh,

Bruce

2023

Front. Aging Neurosci.

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More than 55 million people suffer from dementia, with this number projected to double every 20 years. In the United States, 1 in 3 aged individuals dies from Alzheimer’s disease (AD) or another type of dementia and AD kills more individuals than breast cancer and prostate cancer combined. AD is a complex and multifactorial disease involving amyloid plaque and neurofibrillary tangle formation, glial cell dysfunction, and lipid droplet accumulation (among other pathologies), ultimately leading to neurodegeneration and neuronal death. Unfortunately, the current FDA-approved therapeutics do not reverse nor halt AD. While recently approved amyloid-targeting antibodies can slow AD progression to improve outcomes for some patients, they are associated with adverse side effects, may have a narrow therapeutic window, and are expensive. In this review, we evaluate current and emerging AD therapeutics in preclinical and clinical development and provide insight into emerging strategies that target brain lipid metabolism and microglial function – an approach that may synergistically target multiple mechanisms that drive AD neuropathogenesis. Overall, we evaluate whether these disease-modifying emerging therapeutics hold promise as interventions that may be able to reverse or halt AD progression.

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“…4] Our results of Early-Adult-Deaths 55-74years have received considerable indirect support, from studies on Early-Onset-Dementias (E.O.D) mortality which are reported across the continents, which totally challenges the Gompertzian hypothesis. There are studies showing rising of E.O.D deaths in America [15][16][17][18][19][20] , Europe [21][22][23][24] and China [25][26][27][28][29] . Moreover, there are results from traditionally countries with low neurological morbidity, in South America, and Asia 30--34 .…”

Section: Findings Of Neuro-degenerative Conditions and Environmentmentioning

confidence: 99%

Evidence of Rising Neurological Mortality and Examining Multiple-Interactive Environmental Causes in the 21stCentury

Pritchard

Silk

Hansen

2022

MRAJ

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Aims: To examine whether increased neurological deaths during 21st Century are predominately due to elderly demographics, or major influences of interactive-multiple environmental contributory factors? We examine WHO Early-Adult-Deaths (55-74yearolds), which is below Western life-expectancy, and total Age-Standardised-Death-Rates (ASDR) controlled by age, sex, and population, to challenge the demographic assumption. Method. Based upon WHO latest global neurological mortality categories, Nervous-Disease-Deaths and Alzheimer’s & Other Dementias, which provides the Combined Neurological Death, rates per million (pm), for the twenty-one West-Developed-Nations (WDN) over the period. Early-Adult-Death rates based upon numbers of deaths, divided by 55-74 population and WHO total ASDR during the 21st Century. Increases between Over 75’s population and Over 75’s neurological mortality is compared using Odds Ratios. Numbers of deaths are indicative of family and services pressures. Results: Every country’s 55-74yearolds Nervous-Disease-Deaths rates were higher than Alzheimer’s & Dementia Deaths, ten countries Nervous-Disease-Deaths rose higher than Alzheimer’s & Dementias during Century. Highest Combined Deaths and increases were Finland 1006 per million (pm) up 44%, USA 710pm, rose 39% and UK 653pm a rise of 32%, countries average of 25%, though Belgium, Canada and France rates fell. Highest ASDR were Finland 973pm, up 104%, USA 592pm, rose 76%, UK 553pm, increase 170%. Lowest were Japan 112pm, yet up 90%, Greece 184pm, rose 64% and Austria 214pm increased 102%, average nation’s 62%. Belgium at 387pm up 34%, Canada 401pm, increased 13% and France ASDR 336pm up 11%. Population compared with total neurological amongst Early-Adult-Deaths and Over 75’s, ratios of change, were respectively 1:1.34 and 1:2.21, yielding an Odds ratios of 1:1.65 French total neurological numbers were 40,594 rose to 71,543, up 76%, UK 24,601 to 103,550 increased 321% and the USA 174,708 to 436,438 rising 150%. Discussion: We reject the hypothesis that neurological increases were mainly dues to demographics. Our results support by new studies across the continents, with their findings of significant causal multiple-interactive-environmental pollutants, including, endocrine disruptive chemicals, air pollution, organophosphates, plastics, petrochemicals, impact of low ubiquitous prolonged electro-magnetism, etc, associated with neuro-degenerative disease, especially Early-Onset-Dementia, below Western life-expectancy. Conclusions: Governments should seek urgent research to explain this new epidemic.

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Gene mutations associated with early onset familial Alzheimer’s disease in China: An overview and current status

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 17 publications

References 116 publications

Multi-omics analysis revealed the role of CCT2 in the induction of autophagy in Alzheimer’s disease

Multi-omics analysis revealed the role of CCT2 in the induction of autophagy in Alzheimer’s disease

Emerging Alzheimer’s disease therapeutics: promising insights from lipid metabolism and microglia-focused interventions

Evidence of Rising Neurological Mortality and Examining Multiple-Interactive Environmental Causes in the 21stCentury

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