The autosomal dominant presenilin 1 (PSEN1) E280A mutation is strongly linked to early-onset Alzheimer disease (AD), with carriers typically developing mild cognitive impairment (MCI), rapidly progressing to dementia, before the age of 50 years. However, as recently reported in Nature Medicine, a woman from Colombia with this mutation did not develop MCI until she was in her seventies, despite having a high amyloid-β burden in her brain. The resistance to AD in this individual was attributed to homozygosity for the R136S mutation in the ε3 allele of apolipoprotein E (APOE), also known as the Christchurch or APOE3ch mutation. The beneficial effects of APOE3ch seemed to be mediated through limitation of tau pathology and neurodegeneration. On the basis of these findings, the authors suggested a possible role for APOE modulation in the prevention and treatment of AD.
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06 December 2019
This article has been modified to correct the spelling of Colombia in the title and main text.
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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)
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Wood, H. A single case from Colombia provides insights into Alzheimer disease resistance. Nat Rev Neurol 16, 2 (2020). https://doi.org/10.1038/s41582-019-0293-y
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DOI: https://doi.org/10.1038/s41582-019-0293-y
