• Y Wakutani, K Watanabe, Y Adachi, K Wada-Isoe, K Urakami, H Ninomiya, T C Saido, T Hashimoto, T Iwatsubo, and K Nakashima.
• Department of Neurology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, Yonago, Japan. ywzku@grape.med.tottori-u.ac.jp
• J. Neurol. Neurosurg. Psychiatr. 2004 Jul 1; 75 (7): 1039-42.

ObjectiveTo describe a novel missense mutation, Asp678Asn (D678N), in the amyloid precursor protein (APP) gene in a Japanese pedigree of probable familial Alzheimer's disease (FAD).SubjectThe proband was a women of 72. Symptoms of dementia that fulfilled the criteria for probable Alzheimer's disease appeared at about 60 years of age, and slowly worsened over more than 10 years without evident cerebrovascular complications, either clinically or neuroradiologically.MethodsPolymerase chain reaction single strand conformational polymorphism (PCR-SSCP) analysis followed by sequence analysis was used to examine genomic DNA of the proband for mutations in the APP gene exons 16 and 17.ResultsAnalysis of the APP exon 16 in the proband showed a GAC to AAC nucleotide substitution in codon 678 of the APP gene, causing an amino acid substitution of Asp to Asn (D678N). Heterozygosity of the APP D678N mutation was found in the proband and in the demented elder sister.ConclusionsThe production and accumulation of mutated Abeta (Asn7-Abeta) or the misfunction of D678N mutant APP may have pathogenic properties for the development of Alzheimer's disease in this pedigree.

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