Carriers of the PSEN1E280A mutation overproduce amyloid-β (Aβ) and develop autosomal dominant Alzheimer disease (ADAD) in their forties. However, this study reports that one woman with PSEN1E280A did not show cognitive impairment until her seventies, despite a high burden of Aβ pathology. The woman had two copies of a rare APOE3 allele with a R136S mutation that reduces APOE3’s affinity for heparan sulfate proteoglycans, which have been suggested to promote neuronal uptake of tau. Thus, APOE3R136S might delay ADAD by limiting tau pathology.
References
Original article
Arboleda-Velasquez, J. F. et al. Resistance to autosomal dominant Alzheimer’s disease in an APOE3 Christchurch homozygote: a case report. Nat. Med. 25, 1680–1683 (2019)
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Bray, N. A protective mutation. Nat Rev Neurosci 21, 3 (2020). https://doi.org/10.1038/s41583-019-0246-x
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41583-019-0246-x