ArticlePLoS genetics2013
The PSEN1, p.E318G variant increases the risk of Alzheimer's disease in APOE-ε4 carriers.
Article in PLoS genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 63 citations in OpenAlex.
- Investigation of base excision repair gene variants in late-onset Alzheimer's disease.PloS one · 2019Trial
- GPND-AI NULISA: A 15-Protein AI classifier for diagnosis and co-pathology profiling across neurodegenerative diseases.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- TREM2 as a central hub of neuroimmune-metabolic crosstalk in central nervous system disorders: from microglial biology to therapeutic targeting.Frontiers in immunology · 2026Review
- Overview of Proteomic Analysis of Amyloid Plaques and Neurofibrillary Tangles in Alzheimer's Disease.Biomolecules · 2025Review
- Benchmarking AlphaMissense pathogenicity predictions againstBiochemistry and biophysics reports · 2025Article
- Evaluating pathogenicity of variants of unknown significance in APP, PSEN1, and PSEN2.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Genome-wide association studies identify novel loci in rapidly progressive Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- The ROSMAP project: aging and neurodegenerative diseases through omic sciences.Frontiers in neuroinformatics · 2024Review
- Patient with PSEN1 Glu318Gly and Other Possible Disease Risk Mutations, Diagnosed with Early Onset Alzheimer's Disease.International journal of molecular sciences · 2023Article
- Contributions of rare and common variation to early-onset and atypical dementia risk.medRxiv : the preprint server for health sciences · 2023Article
- The associations of APP, PSEN1, and PSEN2 genes with Alzheimer's disease: A large case-control study in Chinese population.CNS neuroscience & therapeutics · 2023Article
- Dissecting the clinical heterogeneity of early-onset Alzheimer's disease.Molecular psychiatry · 2022Review
- Some Molecular and Cellular Stress Mechanisms Associated with Neurodegenerative Diseases and Atherosclerosis.International journal of molecular sciences · 2021Review
- Amyloid-βAlzheimer's research & therapy · 2020Article
- Evaluation of Animal Models by Comparison with Human Late-Onset Alzheimer's Disease.Molecular neurobiology · 2018Article
- Human fibroblast and stem cell resource from the Dominantly Inherited Alzheimer Network.Alzheimer's research & therapy · 2018Article
- Polygenic risk score of sporadic late-onset Alzheimer's disease reveals a shared architecture with the familial and early-onset forms.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2018Article
- Understanding the roles of mutations in the amyloid precursor protein in Alzheimer disease.Molecular psychiatry · 2018Review
- Parkinson disease polygenic risk score is associated with Parkinson disease status and age at onset but not with alpha-synuclein cerebrospinal fluid levels.BMC neurology · 2017Article
- Exome Sequencing of Extended Families with Alzheimer's Disease Identifies Novel Genes Implicated in Cell Immunity and Neuronal Function.Journal of Alzheimer's disease & Parkinsonism · 2017Article
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
Abstract
The primary constituents of plaques (Aβ42/Aβ40) and neurofibrillary tangles (tau and phosphorylated forms of tau [ptau]) are the current leading diagnostic and prognostic cerebrospinal fluid (CSF) biomarkers for AD. In this study, we performed deep sequencing of APP, PSEN1, PSEN2, GRN, APOE and MAPT genes in individuals with extreme CSF Aβ42, tau, or ptau levels. One known pathogenic mutation (PSEN1 p.A426P), four high-risk variants for AD (APOE p.L46P, MAPT p.A152T, PSEN2 p.R62H and p.R71W) and nine novel variants were identified. Surprisingly, a coding variant in PSEN1, p.E318G (rs17125721-G) exhibited a significant association with high CSF tau (p = 9.2 × 10(-4)) and ptau (p = 1.8 × 10(-3)) levels. The association of the p.E318G variant with Aβ deposition was observed in APOE-ε4 allele carriers. Furthermore, we found that in a large case-control series (n = 5,161) individuals who are APOE-ε4 carriers and carry the p.E318G variant are at a risk of developing AD (OR = 10.7, 95% CI = 4.7-24.6) that is similar to APOE-ε4 homozygous (OR = 9.9, 95% CI = 7.2.9-13.6), and double the risk for APOE-ε4 carriers that do not carry p.E318G (OR = 3.9, 95% CI = 3.4-4.4). The p.E318G variant is present in 5.3% (n = 30) of the families from a large clinical series of LOAD families (n = 565) and exhibited a higher frequency in familial LOAD (MAF = 2.5%) than in sporadic LOAD (MAF = 1.6%) (p = 0.02). Additionally, we found that in the presence of at least one APOE-ε4 allele, p.E318G is associated with more Aβ plaques and faster cognitive decline. We demonstrate that the effect of PSEN1, p.E318G on AD susceptibility is largely dependent on an interaction with APOE-ε4 and mediated by an increased burden of Aβ deposition.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.