We used whole‐exome sequencing to identify variants other than APOE associated with the rate of hippocampal atrophy in amnestic mild cognitive impairment. An in‐silico predicted missense variant in REST (rs3796529) was found exclusively in subjects with slow hippocampal volume loss and validated using unbiased whole‐brain analysis and meta‐analysis across 5 independent cohorts. REST is a master regulator of neurogenesis and neuronal differentiation that has not been previously implicated in Alzheimer's disease. These findings nominate REST and its functional pathways as protective and illustrate the potential of combining next‐generation sequencing with neuroimaging to discover novel disease mechanisms and potential therapeutic targets. Ann Neurol 2015;77:547–552
P4‐335: Integrating whole‐exome sequencing and imaging genetics to identify single‐nucleotide variants associated with rate of hippocampal neurodegeneration in APOE‐ε3/ε3 males with mild cognitive impairment
Alzheimer's & Dementia | March 29, 2014 | Volume: 8 | Issue: 4S_Part_21 | Pages: No page available