Genetic risk scores linked to faster progression to Alzheimer’s
In two observational cohorts, genetic scores were linked to faster progression to Alzheimer’s disease, with hazard ratios, a measure of risk over time, of 1.25 to 2.02.
Alzheimer's & Dementia
In participants from the Alzheimer’s Disease Neuroimaging Initiative and Framingham Heart Study, researchers evaluated genetic risk scores in an observational analysis. They derived the scores from networks of genes whose activity varied together in individual cell nuclei. The analysis identified two genetic risk patterns. One centred on APOE, a gene involved in fat transport; the other was independent of it. Both were associated with faster progression to Alzheimer’s disease, localised brain shrinkage, lower glucose use and greater overall buildup of amyloid protein deposits.
The researchers also prioritised four candidate drugs using network analysis. They tested drugs in astrocytes, brain-support cells grown from human cells reprogrammed into stem cells. Estradiol and levetiracetam reduced activity of APOE and complement C4, a gene involved in immune responses.
Why it matters
Late-onset Alzheimer’s disease varies biologically between people. The framework may help researchers group people by genetic risk when developing more personalised approaches to this age-related disease.
Caveats
The cohort analysis was observational and cannot show that the genetic patterns caused faster progression to Alzheimer’s disease. The drug experiments used lab-grown cells, not patients, and did not test clinical benefit.
The paper
Show 13 more authors
Rufuto Rahman, Daniel Goldstein, Sophia I Thomopoulos, David A Bennett, Lindsay A Farrer, Thor D Stein, Li Shen, Heng Huang, Kwangsik Nho, Andrew J Saykin, Christos Davatzikos, Paul M Thompson, Julia Tcw,Boston University Chobanian and Avedisian School of Medicine
Alzheimer's & Dementia · 1 Oct 2026
