SynthesisActa neuropathologica2016
A comprehensive study of the genetic impact of rare variants in SORL1 in European early-onset Alzheimer's disease.
Synthesis in Acta neuropathologica, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 4 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
60 citing papers in PubMed, 4 syntheses or guidelines pooled it, 115 citations in OpenAlex.
- Finding memo: versatile interactions of the VPS10p-Domain receptors in Alzheimer's disease.Molecular neurodegeneration · 2022Pooled it
- Long Non-coding RNA: Insight Into Mechanisms of Alzheimer's Disease.Frontiers in molecular neuroscience · 2021Pooled it
- Genome-wide rare variant analysis for thousands of phenotypes in over 70,000 exomes from two cohorts.Nature communications · 2020Pooled it
- Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing.Nature genetics · 2019Pooled it
- The Alzheimer's disease risk gene SORL1 is a regulator of excitatory neuronal function.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- SORLA up-regulation suppresses pathological effects in aged tauopathy mouse brain.Science advances · 2026Article
- Alzheimer's disease risk protein SorLA regulates ER homeostasis and lipid metabolism in human microglia, with conserved effects in neurons.Acta neuropathologica · 2026Article
- IsmedRxiv : the preprint server for health sciences · 2026Article
- Domain mapping of disease mutations reveals pathogenic SORL1 variants in Alzheimer's disease.Molecular neurodegeneration · 2025Article
- Whole-genome Sequence Analysis Revealed Novel Subjective Cognitive Decline-associated Genes in 10,763 Chinese.Genomics, proteomics & bioinformatics · 2025Article
- Familial Alzheimer's disease mutation identifies novel role of SORLA in release of neurotrophic exosomes.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Article
- The PKCι-β-arrestin2 axis disrupts SORLA retrograde trafficking, driving its degradation and amyloid pathology in Alzheimer's disease.Molecular neurodegeneration · 2025Article
- The impact of rare genetic variants on Alzheimer disease.Nature reviews. Neurology · 2025Review
- Haploinsufficiency and Alzheimer's Disease: The Possible Pathogenic and Protective Genetic Factors.International journal of molecular sciences · 2024Review
- TheProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Cell type-specific functions of Alzheimer's disease endocytic risk genes.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Review
- A familial missense variant in the Alzheimer's disease gene SORL1 impairs its maturation and endosomal sorting.Acta neuropathologica · 2024Article
- Towards a Unitary Hypothesis of Alzheimer's Disease Pathogenesis.Journal of Alzheimer's disease : JAD · 2024Article
- Mutated Toll-like receptor 9 increases Alzheimer's disease risk by compromising innate immunity protection.Molecular psychiatry · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
28 authors at 10 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The sortilin-related receptor 1 (SORL1) gene has been associated with increased risk for Alzheimer's disease (AD). Rare genetic variants in the SORL1 gene have also been implicated in autosomal dominant early-onset AD (EOAD). Here we report a large-scale investigation of the contribution of genetic variability in SORL1 to EOAD in a European EOAD cohort. We performed massive parallel amplicon-based re-sequencing of the full coding region of SORL1 in 1255 EOAD patients and 1938 age- and origin-matched control individuals in the context of the European Early-Onset Dementia (EOD) consortium, originating from Belgium, Spain, Portugal, Italy, Sweden, Germany, and Czech Republic. We identified six frameshift variants and two nonsense variants that were exclusively present in patients. These mutations are predicted to result in haploinsufficiency through nonsense-mediated mRNA decay, which could be confirmed experimentally for SORL1 p.Gly447Argfs*22 observed in a Belgian EOAD patient. We observed a 1.5-fold enrichment of rare non-synonymous variants in patients (carrier frequency 8.8 %; SkatOMeta p value 0.0001). Of the 84 non-synonymous rare variants detected in the full patient/control cohort, 36 were only detected in patients. Our findings underscore a role of rare SORL1 variants in EOAD, but also show a non-negligible frequency of these variants in healthy individuals, necessitating the need for pathogenicity assays. Premature stop codons due to frameshift and nonsense variants, have so far exclusively been found in patients, and their predicted mode of action corresponds with evidence from in vitro functional studies of SORL1 in AD.
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Registered trials
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.