articleNature MedicineMay 1, 2023HYBRID OA

Resilience to autosomal dominant Alzheimer’s disease in a Reelin-COLBOS heterozygous man

FLFrancisco LoperaCMClaudia MariñoACAnita ChandrahasMOMichael O’HareNDNelson David Villalba‐Moreno

Universidad de Antioquia · Massachusetts Eye and Ear Infirmary · +14 more institutions

PubMed
Indexed incrossrefpubmed

Abstract

We characterized the world's second case with ascertained extreme resilience to autosomal dominant Alzheimer's disease (ADAD). Side-by-side comparisons of this male case and the previously reported female case with ADAD homozygote for the APOE3 Christchurch (APOECh) variant allowed us to discern common features. The male remained cognitively intact until 67 years of age despite carrying a PSEN1-E280A mutation. Like the APOECh carrier, he had extremely elevated amyloid plaque burden and limited entorhinal Tau tangle burden. He did not carry the APOECh variant but was heterozygous for a rare variant in RELN (H3447R, termed COLBOS after the Colombia-Boston biomarker research study), a ligand that like…

Citation impact

189
total citations
FWCI
32.32
Percentile
100%
References
38
Citations per year

Authors

42

Topics & keywords

Topics
Keywords
  • Reelin
  • Presenilin
  • Dementia
  • Alzheimer's disease
  • PSEN1
  • Disease
  • Genetics
  • Biology
No related works found for this paper.

Funding