A new study by researchers from Mass General Brigham further illustrates that when it comes to risk of Alzheimer’s disease, even genetically determined forms of the disease, genetics is only one piece of the puzzle. Researchers investigated the influence of genetics and educational attainment on cognitive decline by studying data from 675 people who carry a mutation that predisposes them to early onset Alzheimer’s disease. Carriers of this mutation—known as PSEN1 E280A—have a median age of 49 for onset of dementia. The team found that among carriers who also carried a second mutation that puts them at heightened risk—APOE e4—had an accelerated age of onset of cognitive decline. Among carriers who had an APOE e2 mutation—known to be protective—age of onset was delayed. The team also assessed the effect of educational attainment on cognitive function among PSEN1 E280A mutation carriers, including those who carried different APOE genotypes. They found that higher educational attainment—that is, more years of education—was associated with preserved cognitive ability particularly for those at highest genetic risk.
“Higher educational attainment may have a protective effect against cognitive impairment, even in the presence of strong genetic risk factors,” said corresponding author Yakeel Quiroz PhD, a clinical neuropsychologist and neuroimaging researcher, director of the Familial Dementia Neuroimaging Lab in the Departments of Psychiatry and Neurology at Massachusetts General Hospital. “Despite the additional risk conferred by APOEe4, the strongest genetic risk factor for sporadic Alzheimer's disease, our results suggest that educational attainment may be a critical mechanism of cognitive reserve in familial Alzheimer’s disease.”
The research team included investigators from Massachusetts General Hospital, Brigham and Women’s Hospital, Mass Eye and Ear, and national and international collaborators.
Read more about the study’s findings in Nature Communications.
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Effect of apolipoprotein genotype and educational attainment on cognitive function in autosomal dominant Alzheimer’s disease
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S.L. is supported by a grant from the Alzheimer’s Association (AARF-22-920754). Y.S. reports grants from The Alzheimer’s Association, The BrightFocus Foundation, NIH/NIA, State of Arizona, outside the submitted work. C.V.-C. reports grants from the Alzheimer’s Association (AARF 2019A005859) and the National Institute on Aging (K99AG073452). K.S.K. is on the Board of Directors for the Tau Consortium, receives funding from the NIA, the Alzheimer Association, and the Alzheimer’s Drug Discovery Foundation. H-S.Y. reports a grant from the National Institute of Aging (K23 AG062750). E.M.R. reports grants from National Institute on Aging (P30 AG072980, R01 AG069453, R01 AG055444), Banner Alzheimer’s Foundation and the NOMIS Foundation during the conduct of the study. E.M.R. is a compensated scientific advisor for Alzheon, Aural Analytics, Denali, Retromer Therapeutics, and Vaxxinity, an uncompensated scientific advisor for Lilly, and a cofounder, advisor and shareholder of AlzPATH, which is involved in the development of blood-based biomarkers for Alzheimer’s disease outside the scope of the submitted. In addition, E.M.R. is the inventor of a patent issued to Banner Health, which involves the use of biomarker endpoints in at-risk persons to accelerate the evaluation of Alzheimer’s disease prevention therapies and is outside the submitted work. F.L. was supported by an Anonymous Foundation, and the Administrative Department of Science, Technology and Innovation (Colciencias Colombia;111565741185). E.M.R. and F.L. are principal investigators of the Alzheimer’s Prevention Initiative (API) Autosomal Dominant AD Trial, which is supported by NIA, philanthropy, Genentech, and Roche. Y.T.Q. was supported by grants from the National Institute on Aging (R01 AG054671, RF1AG077627), the Alzheimer’s Association, and Massachusetts General Hospital ECOR. Y.T.Q. serves as consultant for Biogen. The remaining authors declare no competing interests.