A novel W165G mutation in the presenilin-1 (PS1) gene has been identified in a clinically diagnosed Alzheimer's disease (AD) patient from an early-onset Japanese AD family. Although the segregation pattern of the mutation in this family has not yet been confirmed, the clinical characteristics, family history, position of the heterozygous mutation in the PS1 gene, and absence of the mutation in 207 early-onset and late-onset AD patients and 200 normal elderly controls strongly suggest that this mutation is causative of the AD phenotype. The course of the disease in this patient was aggressive. Rapid cognitive decline, decreased blood flow in the parieto-occucipital region, and significantly increased tau protein in the cerebrospinal fluid were observed within 3 years of AD onset at the age of 38 years. The non-conservative W165G amino acid replacement is hypothesized to cause substantial changes in both the structure and function of the PS1 protein, leading to AD.
|Number of pages||5|
|Publication status||Published - 2000|
ASJC Scopus subject areas
- Clinical Neurology