Resistance to autosomal dominant Alzheimer's disease in an APOE3 Christchurch homozygote: a case report

Nat Med. 2019 Nov;25(11):1680-1683. doi: 10.1038/s41591-019-0611-3. Epub 2019 Nov 4.

Abstract

We identified a PSEN1 (presenilin 1) mutation carrier from the world's largest autosomal dominant Alzheimer's disease kindred, who did not develop mild cognitive impairment until her seventies, three decades after the expected age of clinical onset. The individual had two copies of the APOE3 Christchurch (R136S) mutation, unusually high brain amyloid levels and limited tau and neurodegenerative measurements. Our findings have implications for the role of APOE in the pathogenesis, treatment and prevention of Alzheimer's disease.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Amyloid / genetics
  • Amyloid / metabolism
  • Apolipoprotein E2 / genetics
  • Apolipoprotein E3 / genetics*
  • Brain / diagnostic imaging
  • Brain / metabolism
  • Brain / pathology
  • Cognitive Dysfunction / genetics
  • Cognitive Dysfunction / pathology
  • Female
  • Homozygote
  • Humans
  • Male
  • Mutation / genetics
  • Neurodegenerative Diseases / genetics*
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / pathology
  • Pedigree
  • Presenilin-1 / genetics*

Substances

  • Amyloid
  • Apolipoprotein E2
  • Apolipoprotein E3
  • PSEN1 protein, human
  • Presenilin-1