Amyloid load in nondemented brains correlates with APOE e4.

Area of Science:

• Neuropathology
• Genetics
• Neurodegenerative Diseases

Background:

• The apolipoprotein E (APOE) e4 allele is a known genetic risk factor for Alzheimer's disease.
• Understanding its impact on specific neuropathological hallmarks is crucial for disease mechanism research.

Purpose of the Study:

• To investigate the association between APOE e4 carriage and neuropathological markers in cognitively healthy older adults.
• To compare amyloid plaque density, congophilic amyloid angiopathy (CAA), and neurofibrillary tangle (NFT) density between APOE e4 carriers and non-carriers.

Main Methods:

• Analysis of post-mortem brain tissue from 179 adults (≥60 years) from the Sun Health Brain Donation program.
• Quantification of amyloid plaque density, CAA, and NFT density using CERAD criteria.
• Comparison of neuropathological scores between APOE e4 carriers (n=42) and non-carriers (n=137).

Main Results:

• APOE e4 carriers exhibited significantly higher total plaque density and CAA burden compared to non-carriers.
• This difference in amyloid pathology was consistent across examined brain subregions.
• No significant differences were observed in neuritic plaque or NFT density between APOE e4 carriers and non-carriers.

Conclusions:

• Cognitively healthy APOE e4 carriers over 60 have an increased burden of parenchymal and vascular amyloid neuropathology.
• The APOE e4 genotype influences amyloid deposition but not tau pathology (NFTs) in this non-demented cohort.
• Findings highlight genotype-specific effects on Alzheimer's disease-related pathologies.