| Title: | How does type 2 diabetes modify the risk of Alzheimer's disease? |
| Journal: | Alzheimer's & Dementia |
| Published: | 18 May 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42151730/ |
| DOI: | https://doi.org/10.1002/alz.71471 |
Publication 20000
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Abstract
Type 2 diabetes (T2D) and Alzheimer's disease (AD) are both increasing exponentially worldwide. T2D has also been identified as one of 14 modifiable risk factors for dementia, but the mechanism is unknown. T2D could promote dementia via vascular or AD neuropathological changes, and mechanistic hypotheses include central insulin resistance and T2D's peripheral inflammation promoting central inflammation. Here we examine these different hypotheses by reviewing the recent literature in combination with re-analysis of post mortem brain tissue molecular data. Collectively, recent studies and single-cell transcriptomic data suggest that peripheral lipid anomalies and inflammation seen in T2D act together to reduce brain-blood barrier integrity, facilitating aberrant immune signaling between the periphery and the brain. The subsequent promotion of AD-specific microglial subtypes is the most likely mechanism linking T2D and AD. These AD-specific microglial subtypes may be reduced by therapeutic targeting of triggering receptor expressed on myeloid cells 2-apolipoprotein E signaling pathway.</p>
10 Keywords
- Alzheimer Disease
- Apolipoproteins E
- Blood-Brain Barrier
- Brain
- Diabetes Mellitus, Type 2
- Humans
- Inflammation
- Insulin Resistance
- Microglia
- Risk Factors
8 Authors
- G. T. Sutherland
- A. Chen
- H-T. Nguyen-Hao
- H. Mundell
- E. Aladyeva
- M. J. Hofer
- O. Harari
- S. M. Twigg
1 Application
| Application ID | Title |
|---|---|
| 49777 | Identification of genetic and lifestyle risk factors of unhealthy brain ageing to direct mechanistic studies using post-mortem brain tissue |
Enabling scientific discoveries that improve human health