| Title: | Obesity-related brain atrophy is independent of Alzheimer's disease protein pathways |
| Journal: | Journal of Alzheimer's Disease |
| Published: | 27 Jul 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40717444/ |
| DOI: | https://doi.org/10.1177/13872877251359680 |
Publication 16091
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Abstract
BackgroundObesity increases the risk for Alzheimer's disease (AD) and other dementias. Obesity causes structural brain injury, and it has been suggested that this may contribute to the development of AD pathology. Neurodegeneration in AD results from the aggregation of misfolded and dysfunctional tau and amyloid-β. However, it remains unknown whether adiposity-related brain injury acts through tau and amyloid deposition or as an independent cause of neurodegeneration.ObjectiveHere, we tested whether obesity, cerebrovascular disease, and obesity-related metabolic risk score were associated with structural brain and cognitive changes via the same mechanisms as AD or independent of them.MethodsWe used the UK Biobank sample of over 33,000 individuals aged 64 years on average. We tested the influence of the microtubule-associated protein tau (MAPT) and apolipoprotein E (APOE) risk alleles involved in tau and amyloid-β synthesis, folding, and clearance, as well as AD polygenic risk score (PRS) to define genetic risk of AD. Specifically, we investigated whether these genetic risk factors moderated the relationship between obesity and brain structure and cognition.ResultsWe found that MAPT and APOE status and AD PRS did not moderate the relationship between obesity and brain atrophy. We also found limited evidence for the moderation of MAPT and APOE of the cerebrovascular disease-brain structure relationship as well as the metabolic risk score-brain structure relationship.ConclusionsWe conclude that the mechanisms linking obesity with brain atrophy are most likely independent of the ones governing AD-related protein deposition.</p>
14 Keywords
- Aged
- Aged, 80 and over
- Alzheimer Disease
- Apolipoproteins E
- Atrophy
- Brain
- Female
- Humans
- Magnetic Resonance Imaging
- Male
- Middle Aged
- Obesity
- Risk Factors
- tau Proteins
5 Authors
- Filip Morys
- Lang Liu
- Konstantin Senkevich
- Ziv Gan-Or
- Alain Dagher
1 Application
| Application ID | Title |
|---|---|
| 45551 | Mechanistic modelling of neurodevelopment, neuroplasticity, and neurodegeneration |
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