APOE gene variation associated with accelerated brain atrophy

Presence of the epsilon 4 variant of the apolipoprotein E (APOE) gene has been associated with accelerated rates of brain atrophy in individuals with mild cognitive impairment (MCI), according to a study published online Jan. 14 in Radiology.

The variation is associated with a higher risk for development of Alzheimer’s disease (AD), earlier age of onset and faster progression, according to Jeffrey R. Petrella, MD, of Duke University School of Medicine in Durham, N.C., and colleagues.

APOE is the most important genetic factor known in non-familial AD. Everyone carries two APOE alleles, and the researchers noted that most people have at least one copy of the APOE epsilon 3 variant, which is neutral with regards to Alzheimer’s risk.

For the current study, Petrella and colleagues analyzed data from 237 patients with MCI in the Alzheimer’s Disease Neuroimaging Initiative. Mean age of the patients was nearly 80. MRI was used to measure brain atrophy rates over a 1-4 year period.

Results showed epsilon 4 carriers had significantly greater atrophy rates when compared with epsilon 3 carriers in 13 out of 15 brain regions associated with AD, even though the patients did not yet have AD. “This suggests the possibility of a genotype-specific network of related brain regions that undergo faster atrophy in MCI and potentially underlies the observed cognitive decline,” said Petrella in a press release.

While the study did not look at why APOE epsilon 4 may accelerate atrophy, the researchers suggested it may be connected to APOE’s role in breaking down beta-amyloid proteins associated with AD.

The finding could influence clinical trial design as epsilon 4 carriers could be added to study population to better monitor treatment response in vulnerable regions.