Gene

Apolipoprotein E

Biology

Amyloid (mycology)

Mutation

Alzheimer's disease

PSEN1

Genetics

Early-onset Alzheimer's disease

Internal medicine

Dementia

Presenilin

Medicine

Disease

Pathogenesis

Pathology

Nature Medicine

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. A unique case from the Colombian cohort of autosomal dominant Alzheimer’s disease is reported in which disease progression is substantially delayed despite unusually high amyloid plaque pathology, possibly related to a rare mutation in APOE3.

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