Abstract:
: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.
journal_name
Aging Celljournal_title
Aging cellauthors
Sebastiani P,Monti S,Morris M,Gurinovich A,Toshiko T,Andersen SL,Sweigart B,Ferrucci L,Jennings LL,Glass DJ,Perls TTdoi
10.1111/acel.13023subject
Has Abstractpub_date
2019-12-01 00:00:00pages
e13023issue
6eissn
1474-9718issn
1474-9726journal_volume
18pub_type
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