A mutation in the amyloid precursor protein associated with hereditary Alzheimer's disease.
Alzheimer's disease is a form of localized amyloidosis characterized by cerebral cortical amyloid plaques, neurofibrillary tangles, and amyloid deposits within the walls of leptomeningeal vessels. Although most cases of Alzheimer's disease are sporadic, kindreds with autosomal-dominant inheritance of the syndrome suggest that a single mutation may be important in pathogenesis. Direct sequencing of DNA from a family with autopsy-proven Alzheimer's disease revealed a single amino acid substitution (Phe for Val) in the transmembrane domain of the amyloid precursor protein. This mutation correlates with the presence of Alzheimer's disease in all patients in this study, and may be the inherited factor causing both amyloid fibril formation and dementia.
Murrell
J
J
Indiana University School of Medicine, Department of Medicine.
Farlow
M
M
Ghetti
B
B
Benson
M D
MD
D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology; D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005091:Exons; D006801:Humans; D008969:Molecular Sequence Data; D016874:Neurofibrillary Tangles / Q000473:pathology; D010375:Pedigree; D016133:Polymerase Chain Reaction
D016564:Amyloid beta-Protein Precursor