A recent history of failed clinical trials suggests that waiting until even the early stages of onset of Alzheimer's disease may be too late for effective treatment, pointing to the importance of early intervention in young people. Early intervention will require markers of Alzheimer's risk that track with genotype but are capable of responding to treatment. Here, we sought to identify a functional MRI signature of combined Alzheimer's risk imparted by two genetic risk factors. We used a task of executive attention during fMRI in participants genotyped for two Alzheimer's risk alleles: APOE-ε4 and CLU-C. Executive attention is a sensitive indicator of the progression of Alzheimer's even in the early stages of mild cognitive impairment, but has not yet been investigated as a marker of Alzheimer's risk in young adults. Functional MRI revealed that APOE-ε4 and CLU-C had an additive effect on brain activity such that increased combined genetic risk was associated with decreased brain activity during executive attention, including in the medial temporal lobe, a brain area affected early in Alzheimer's pathogenesis.
|Original language||English (US)|
|Number of pages||8|
|State||Published - Apr 2014|
Bibliographical noteFunding Information:
This work was supported by NIH R01 AG035379 , P01 AG030128 (GWR), NSF DRL 0644131 (JRG) and NSF REC 0634025 (JRG), and a grant from Partners in Research (TRM and AEG). Samples from the National Cell Repository for Alzheimer's Disease (NCRAD) , which receives government support under a cooperative agreement grant ( U24 AG21886 ) awarded by the National Institute on Aging (NIA), were used in this study. We wish to thank M.H.E. Johnson and D.P. Kraemer for thoughtful comments on an earlier version of the manuscript.
- Executive attention
- Medial temporal lobe