APOE, TOMM40, and sex interactions on neural network connectivity

Li, Tianqi; Pappas, Colleen; Le, Scott T.; Wang, Qian; Klinedinst, Brandon S.; Larsen, Brittany; Pollpeter, Amy; Lee, Ling Yi; Lutz, Michael W.; Gottschalk, William K.; Swerdlow, Russell H.; Nho, Kwangsik; Willette, Auriel A.

doi:10.1016/j.neurobiolaging.2021.09.020

Cited by 13 publications

(20 citation statements)

References 56 publications

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“…Owing to the linkage disequilibrium with APOE (Simonovitch et al, 2019 ), TOMM40 expression is closely associated with APOE expression (Mise et al, 2017 ), and APOE - TOMM40 - APOC1 variants are strongly associated with a high instance of AD (Gottschalk et al, 2014 ; Kulminski et al, 2022 ). With increasing age, APOE ε4 has closely linked to various TOMM40 polymorphisms carried adverse impacts (Roses et al, 2013 ; Li et al, 2022 ), and alter the distribution and function of the TOMM40 haplotypes (Roses et al, 2010 ). which echoes the mentioned findings—more FL-PINK1 and Parkin, less cleaved PINK1 caused by ApoE4 (Simonovitch et al, 2019 ).…”

Section: Apoe4 and Mitophagy-specific Processes In Admentioning

confidence: 99%

A Review of ApoE4 Interference Targeting Mitophagy Molecular Pathways for Alzheimer's Disease

Chen

Jiang

et al. 2022

Front. Aging Neurosci.

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Alzheimer's disease (AD) is one of the major worldwide causes of dementia that is characterized by irreversible decline in learning, memory loss, and behavioral impairments. Mitophagy is selective autophagy through the clearance of aberrant mitochondria, specifically for degradation to maintain energy generation and neuronal and synaptic function in the brain. Accumulating evidence shows that defective mitophagy is believed to be as one of the early and prominent features in AD pathogenesis and has drawn attention in the recent few years. APOE ε4 allele is the greatest genetic determinant for AD and is widely reported to mediate detrimental effects on mitochondria function and mitophagic process. Given the continuity of the physiological process, this review takes the mitochondrial dynamic and mitophagic core events into consideration, which highlights the current knowledge about the molecular alterations from an APOE-genotype perspective, synthesizes ApoE4-associated regulations, and the cross-talk between these signaling, along with the focuses on general autophagic process and several pivotal processes of mitophagy, including mitochondrial dynamic (DRP1, MFN-1), mitophagic induction (PINK1, Parkin). These may shed new light on the link between ApoE4 and AD and provide novel insights for promising mitophagy-targeted therapeutic strategies for AD.

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Section: Apoe4 and Mitophagy-specific Processes In Admentioning

confidence: 99%

A Review of ApoE4 Interference Targeting Mitophagy Molecular Pathways for Alzheimer's Disease

Chen

Jiang

et al. 2022

Front. Aging Neurosci.

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“…Half of the studies were exploratory studies such as Genome-Wide Association Studies (GWAS) and SNP panels [ 7 , 10 –, 28 – 35 ]. The remaining studies [ 36 –, 37 – 49 ] specifically selected a TOMM40 SNP or SNPs of interest. Sixteen unique SNPs were investigated in the studies.…”

Section: Resultsmentioning

confidence: 99%

“…Nine studies investigated the effect of TOMM40 SNPs on cognitive ability among individuals without AD [ 31 , 32 , 35 , 37 , 42 , 44 , 46 , 48 , 49 ]. The evaluations differed across research studies but were mainly focused on episodic memory performances and verbal/vocabulary abilities.…”

Section: Resultsmentioning

confidence: 99%

“…BMI [ 33 , 38 ]; Cognitive Function [ 31 , 49 ]; Longevity [ 7 , 10 , 29 , 30 , 34 , 40 , 41 , 45 ];…”

Section: Resultsmentioning

confidence: 99%

“…Two reviewed articles pointed out that the rs2075650-g allele is linked to weakened verbal ability in non-AD individuals. Arpawong et al reported an association with delayed verbal recall ability [ 31 ]; and Li et al reported an overall decrease in language comprehension network strength in the female population, correlated with increasing age [ 49 ]. It has also been suggested that rs2075650 has a strong association with AD, with an odds ratio of 4.178 ( p -value = < 0.001) in Asian and Caucasian populations [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

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TOMM40 genetic variants associated with healthy aging and longevity: a systematic review

et al. 2022

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Introduction Healthy aging relies on mitochondrial functioning because this organelle provides energy and diminishes oxidative stress. Single nucleotide polymorphisms (SNPs) in TOMM40, a critical gene that produces the outer membrane protein TOM40 of mitochondria, have been associated with mitochondrial dysfunction and neurodegenerative processes. Yet it is not clear whether or how the mitochondria may impact human longevity. We conducted this review to ascertain which SNPs have been associated with markers of healthy aging. Methods Using the PRISMA methodology, we conducted a systematic review on PubMed and Embase databases to identify associations between TOMM40 SNPs and measures of longevity and healthy aging. Results Twenty-four articles were selected. The TOMM40 SNPs rs2075650 and rs10524523 were the two most commonly identified and studied SNPs associated with longevity. The outcomes associated with the TOMM40 SNPs were changes in BMI, brain integrity, cognitive functions, altered inflammatory network, vulnerability to vascular risk factors, and longevity. Discussions Our systematic review identified multiple TOMM40 SNPs potentially associated with healthy aging. Additional research can help to understand mechanisms in aging, including resilience, prevention of disease, and adaptation to the environment.

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Common and unique brain aging patterns between females and males quantified by large‐scale deep learning

Du,

Yuan,

Sui

et al. 2024

Human Brain Mapping

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There has been extensive evidence that aging affects human brain function. However, there is no complete picture of what brain functional changes are mostly related to normal aging and how aging affects brain function similarly and differently between males and females. Based on resting‐state brain functional connectivity (FC) of 25,582 healthy participants (13,373 females) aged 49–76 years from the UK Biobank project, we employ deep learning with explainable AI to discover primary FCs related to progressive aging and reveal similarity and difference between females and males in brain aging. Using a nested cross‐validation scheme, we conduct 4200 deep learning models to classify all paired age groups on the main data for females and males separately and then extract gender‐common and gender‐specific aging‐related FCs. Next, we validate those FCs using additional 21,000 classifiers on the independent data. Our results support that aging results in reduced brain functional interactions for both females and males, primarily relating to the positive connectivity within the same functional domain and the negative connectivity between different functional domains. Regions linked to cognitive control show the most significant age‐related changes in both genders. Unique aging effects in males and females mainly involve the interaction between cognitive control and the default mode, vision, auditory, and frontoparietal domains. Results also indicate females exhibit faster brain functional changes than males. Overall, our study provides new evidence about common and unique patterns of brain aging in females and males.

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APOE, TOMM40, and sex interactions on neural network connectivity

Cited by 13 publications

References 56 publications

A Review of ApoE4 Interference Targeting Mitophagy Molecular Pathways for Alzheimer's Disease

A Review of ApoE4 Interference Targeting Mitophagy Molecular Pathways for Alzheimer's Disease

TOMM40 genetic variants associated with healthy aging and longevity: a systematic review

Common and unique brain aging patterns between females and males quantified by large‐scale deep learning

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