Early-onset Alzheimer's disease caused by mutations at codon 717 of the β-amyloid precursor protein gene
Abstract
A mutation at codon 717 of the beta-amyloid precursor protein gene has been found to cosegregate with familial Alzheimer's disease in a single family. This mutation has been reported in a further five out of approximately 100 families multiply affected by Alzheimer's disease. We have identified another family, F19, in which we have detected linkage between the beta-amyloid precursor protein gene and Alzheimer's disease. Direct sequencing of exon 17 in affected individuals from this family has revealed a base change producing a Val----Gly substitution, also at codon 717. The occurrence of a second allelic variant at codon 717 linked to the Alzheimer's phenotype supports the hypothesis that they are pathogenic mutations.
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Early onset Alzheimer's disease can be caused by mutations in the APP, presenilin 1, and presenilin 2 genes.
“Early onset Alzheimer's disease can be caused by mutations in the APP (Chartier-Harlin et al., 1991;Goate et al., 1991;Murrell et al., 1991;Mullan et al., 1992), presenilin 1 (PS1) (Sherrington et al., 1995), and presenilin 2 (PS2) (Levy-Lahad et al., 1995) genes.”
From Age-Dependent Changes in Brain, CSF, and Plasma Amyloid β Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease (2001) · cites this paper as Chartier-Harlin et al., 1991
The number and morphology of dendritic spines remain dynamic and are ultimately distorted in disease.
“Even beyond early embryonic development, the number and morphology of dendritic spines remain dynamic and are ultimately distorted in disease.30,31”
From The lysosome and proteostatic stress at the intersection of pediatric neurological disorders and adult neurodegenerative diseases (2025) · cites this paper as [30]
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Self-citation
- Authors
- Chartier-Harlin, M.-C., Crawford, F., Houlden, H., Warren, A., Hughes, D., Fidani, L., Goate, A., Rossor, M., Roques, P., Hardy, J., & Mullan, M.
- Affiliations
- St Mary's Hospital (GB)
- Venue
- Nature
- Published
- 1991-10
- Volume
- 353
- Issue
- 6347
- Pages
- 844-846
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2081569845
- Cited by
- 1,214
- References
- 0
- Citations by year
- 2026: 15 · 2025: 17 · 2024: 23 · 2023: 16 · 2022: 17 · 2021: 28 · 2020: 22 · 2019: 32 · 2018: 20 · 2017: 22 · 2016: 31 · 2015: 22 · 2014: 27 · 2013: 20 · 2012: 32
- FWCI
- 67.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- early-onset Alzheimer's disease, familial Alzheimer's disease, genetic linkage, co-segregation, pathogenic variants, allelic variants, exon 17
- MeSH terms
- Alzheimer Disease, Amino Acid Sequence, Base Composition, Base Sequence, Codon, Exons, Female, Genes, Humans, Male, Molecular Sequence Data, Mutation, Oligodeoxyribonucleotides, Pedigree, Polymerase Chain Reaction, Amyloid beta-Protein Precursor
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