A pathogenic mutation for probable Alzheimer's disease in the APP gene at the N–terminus of β–amyloid
- 1 August 1992
- journal article
- case report
- Published by Springer Nature in Nature Genetics
- Vol. 1 (5) , 345-347
- https://doi.org/10.1038/ng0892-345
Abstract
Mutations at codon 717 in exon 17 of the β–amyloid precursor protein (APP) gene have previously been shown to segregate with early onset Alzheimer's disease in some families. We have identified a double mutation at codons 670 and 671 (APP 770 transcript) in exon 16 which co–segregates with the disease in two large (probably related) early–onset Alzheimer's disease families from Sweden. Two base pair transversions (G to T, A to C) from the normal sequence predict Lys to Asn and Met to Leu amino acid substitutions at codons 670 and 671 of the APP transcript. This mutation occurs at the amino terminal of β–amyloid and may be pathogenic because it occurs at or close to the endosomal/lysosomal cleavage site of the molecule. Thus, pathogenic mutations in APP frame the β–amyloid sequence.Keywords
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