The discovery of treatments to prevent or delay
dementia and
Alzheimer's disease is a priority. The gene
APOE is associated with cognitive change and late-onset
Alzheimer's disease, and epidemiological studies have provided strong evidence that the e2 allele of
APOE has a
neuroprotective effect, it is associated with increased longevity and an extended healthy lifespan in centenarians. In this study, we correlated
APOE genotype data of 222 participants of the New England Centenarian Study, including 75 centenarians, 82 centenarian offspring, and 65 controls, comprising 55 carriers of
APOE e2 , with aptamer-based serum proteomics (SomaLogic technology) of 4,785 human
proteins corresponding to 4,137 genes. We discovered a signature of 16
proteins that associated with different
APOE genotypes and replicated the signature in three independent studies. We also show that the
protein signature tracks with gene expression profiles in brains of late-onset
Alzheimer's disease versus healthy controls. Finally, we show that seven of these
proteins correlate with cognitive function patterns in longitudinally collected data. This analysis in particular suggests that Baculoviral IAP repeat containing two (BIRC2) is a novel
biomarker of neuroprotection that associates with the neuroprotective allele of
APOE. Therefore, targeting
APOE e2 molecularly may preserve cognitive function.