Understanding apolipoprotein E as a predominant cause of Alzheimer's disease.

Authors

Dylan M Williams, Naaheed Mukadam, Neil M Davies, Emma L Anderson

Published in

Brain : a journal of neurology. Nov 11, 2026. Epub Nov 11, 2026.

Abstract

The full contribution of apolipoprotein E (APOE) to Alzheimer's disease burden in populations may have been overlooked. This is due, in large part, to a lack of recognition that the most common allele of the APOE gene, ε3, increases risk of Alzheimer's disease relative to the ε2 allele. When the impact of both ε3 and ε4 alleles of APOE are considered, the majority of late-onset Alzheimer's disease appears to be attributable to differences in APOE function or expression in populations of European ancestry and in other ethnic groups for which we have reliable data. Moreover, most sporadic early-onset Alzheimer's disease might not occur without the contributions of APOE ε3 and ε4, and the two alleles may be component causes of most forms of Alzheimer's disease arising from highly penetrant genetic mutations and trisomy 21. Taken together, these lines of epidemiological evidence suggest that APOE is a predominant cause of Alzheimer's disease, spanning the aetiologies of many forms of the disease. Consequently, almost all prospective cases of Alzheimer's disease might benefit from the development of therapies to modulate APOE's role in the disease's pathophysiology.

PMID:
43017815
Bibliographic data and abstract were imported from PubMed on 12 Nov 2026.

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