Novel amyloid precursor protein gene missense mutation (D678N) in probable familial Alzheimer’s disease
- Y Wakutani1,
- K Watanabe2,
- Y Adachi1,
- K Wada-Isoe1,
- K Urakami3,
- H Ninomiya4,
- T C Saido6,
- T Hashimoto5,
- T Iwatsubo5,
- K Nakashima1
- 1Department of Neurology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, Yonago, Japan
- 2Watanabe Hospital, Tottori, Japan
- 3Department of Biological Regulation, School of Health Science, Faculty of Medicine, Tottori University, Yonago, Japan
- 4Department of Neurobiology, School of Life Sciences, School of Health Science, Faculty of Medicine, Tottori University, Yonago, Japan
- 5Department of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan
- 6Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Wako-shi, Japan
- Correspondence to: Dr Y Wakutani Department of Neurology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, 36-1 Nishimachi, Yonago, 683-8504, Japan;
- Received 21 January 2003
- Accepted 12 October 2003
- Revised 7 October 2003
Objective: To 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).
Subject: The 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.
Methods: Polymerase 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.
Results: Analysis 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.
Conclusions: The 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.
- Abeta, amyloid β peptide
- APP, amyloid precursor protein
- FAD, familial Alzheimer’s disease
- PCR-SSCP, polymerase chain reaction single strand conformational polymorphism
- amyloid precursor protein
- D678N mutation
- familial Alzheimer’s disease
- single photon computed emission tomography
Competing interests: none declared