How the APOE4 gene damages brain blood vessels in Alzheimer's disease

A recent study analyzing data from the AMYPAD Prognostic Natural History Study has found that amyloid-beta accumulation in the brains of older individuals can predict future brain atrophy before any dementia symptoms appear. This research, published in NeuroImage: Clinical, involved 1,329 participants aged 50 and above, with 56% being women and 40% carrying at least one version of the APOE-ε4 gene, which is linked to an increased risk of Alzheimer's disease.

The study used magnetic resonance imaging (MRI) and positron emission tomography (PET) to scan the brains of participants, with 684 undergoing a second scan within three years. On average, participants experienced brain volume reduction over time, particularly in the temporal, parietal, hippocampus, and amygdala regions. Similarly, cortical thickness decreased in these areas.

Higher amyloid-beta concentrations were linked to smaller volumes and thinner cortices in these regions. The strongest effects were seen in the posterior cingulate, fusiform, and parahippocampal gyri, along with the hippocampus and amygdala. Importantly, the study found that fusiform atrophy was predicted by amyloid-beta independently of tau protein levels, and this association was more pronounced in women when temporal regions were considered.

For individuals with the APOE-ε4 gene, these associations were stronger in the frontal and lateral-temporal regions and the hippocampus. The research suggests that baseline amyloid PET scans could serve as sensitive markers to identify early Aβ-related neurodegeneration and help stratify risk in Alzheimer's disease prevention trials. However, the study's design does not allow for causal inferences to be made from the results.