ArticleNeurology2012
Role of common and rare APP DNA sequence variants in Alzheimer disease.
Article in Neurology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 3 of them syntheses that pooled it.
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Who cites it
50 citing papers in PubMed, 3 syntheses or guidelines pooled it, 83 citations in OpenAlex.
- Guidelines for bioinformatics of single-cell sequencing data analysis in Alzheimer's disease: review, recommendation, implementation and application.Molecular neurodegeneration · 2022Pooled it
- The Amyloid-β Pathway in Alzheimer's Disease.Molecular psychiatry · 2021Pooled it
- Copy Number Variants in Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2017Pooled it
- Centralized Review of Alzheimer's Disease and Related Dementias Biomedical Repositories and Computational Methods.Bioengineering (Basel, Switzerland) · 2026Review
- Small-Molecule Targeting of the Iron-Responsive Element in the APP mRNA 5'-UTR to Control Amyloid Translation in Alzheimer's Disease.International journal of molecular sciences · 2026Review
- Structural variation detection and association analysis of whole-genome-sequence data from 16,543 Alzheimer's disease sequencing project subjects.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Structural variants linked to Alzheimer's disease and other common age-related clinical and neuropathologic traits.Genome medicine · 2025Article
- Structural variants linked to Alzheimer's Disease and other common age-related clinical and neuropathologic traits.medRxiv : the preprint server for health sciences · 2024Article
- Review
- Emerging Perspectives on Prime Editor Delivery to the Brain.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Physiopathological mechanisms underlying Alzheimer's disease: a narrative review.Dementia & neuropsychologia · 2024Review
- Anti-Amyloid Therapies for Alzheimer's Disease and the Amyloid Cascade Hypothesis.International journal of molecular sciences · 2023Review
- SCING: Inference of robust, interpretable gene regulatory networks from single cell and spatial transcriptomics.iScience · 2023Article
- Aggregation of Disordered Proteins Associated with Neurodegeneration.International journal of molecular sciences · 2023Review
- Brain Region-Dependent Alternative Splicing of Alzheimer Disease (AD)-Risk Genes Is Associated With Neuropathological Features in AD.International neurourology journal · 2022Article
- Molecular mechanisms of amyloid formation in living systems.Chemical science · 2022Review
- Rodent Modeling of Alzheimer's Disease in Down Syndrome:Frontiers in neuroscience · 2022Review
- The role of structural variations in Alzheimer's disease and other neurodegenerative diseases.Frontiers in aging neuroscience · 2022Review
- PeakCNV: A multi-feature ranking algorithm-based tool for genome-wide copy number variation-association study.Computational and structural biotechnology journal · 2022Article
- Mutations in SORL1 and MTHFDL1 possibly contribute to the development of Alzheimer's disease in a multigenerational Colombian Family.PloS one · 2022Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
objectivesMore than 30 different rare mutations, including copy number variants (CNVs), in the amyloid precursor protein gene (APP) cause early-onset familial Alzheimer disease (EOFAD), whereas the contribution of common APP variants to disease risk remains controversial. In this study we systematically assessed the role of both rare and common APP DNA variants in Alzheimer disease (AD) families.
methodsFamilies with EOFAD genetically linked to the APP region were screened for missense mutations and locus duplications of APP. Further, using genome-wide DNA microarray data, we examined the APP locus for CNVs in a total of 797 additional early- and late-onset AD pedigrees. Finally, 423 single nucleotide polymorphisms (SNPs) in the APP locus, including 2 promoter polymorphisms previously associated with AD risk, were tested in up to 4,200 individuals from multiplex AD families.
resultsAnalyses of 8 21q21-linked families revealed one family carrying a nonsynonymous mutation in exon 17 (Val717Leu) and another family with a partially penetrant 3.5-Mb locus duplication encompassing APP. CNV analysis in the APP locus revealed an additional family carrying a fully penetrant 380-kb duplication, merely spanning APP. Last, contrary to previous reports, association analyses of more than 400 different SNPs in or near APP failed to show significant effects on AD risk.
conclusionOur study shows that APP mutations and locus duplications are a very rare cause of EOFAD and that the contribution of common APP variants to AD susceptibility is insignificant. Furthermore, duplications of APP may not be fully penetrant, possibly indicating the existence of hitherto unknown protective genetic factors.
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