A LARGE SWEDISH FAMILY WITH ALZHEIMERS-DISEASE WITH A CODON-670 671 AMYLOID PRECURSOR PROTEIN MUTATION - A CLINICAL AND GENEALOGICAL INVESTIGATION/

Objective: To describe clinical and genealogic features in a Swedish f amily with Alzheimer's disease with a double mutation of the amyloid p recursor protein gene at codon 670/671 and to study the effects of ant icipation and imprinting. Design: Interviews with relatives, clinical investigations of the disease, pedigree analysis, studies of medical r ecords, and comparison with other families affected by Alzheimer's dis ease with amyloid precursor protein mutations. Setting: The Alzheimer' s Disease Research Centre, Department of Clinical Neuroscience, Sectio n of Geriatric Medicine, Karolinska Institute, Huddinge (Sweden) Unive rsity Hospital. Patients and Other Participants: Individuals with the amyloid precursor protein codon 670/671 mutation and their relatives ( N=66). Results: The trait was traced through eight generations, and an autosomal dominant inheritance with very high penetrance was observed . Onset occurred between 44 and 61 years of age (mean, 53 years). The mean duration of disease was 8.5 years (range, 3 to 13 years). The ear liest clinical manifestations were deficits in memory function and abs tract reasoning. Myoclonic jerks and seizures were common symptoms lat e in the disease. Anticipation and imprinting effects were not found i n this family. Conclusions: The disease in this family has a single or igin-a double mutation in the amyloid precursor protein gene at codon 670/671 transmitted as an autosomal dominant trait. The wide range in age at onset and the clinical symptoms in this pedigree give a charact eristic phenotype similar to that seen in some of the other pedigrees with amyloid precursor protein mutations.