ReviewMolecular neurodegeneration2022
Challenge accepted: uncovering the role of rare genetic variants in Alzheimer's disease.
Review in Molecular neurodegeneration, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 27 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
27 citing papers in PubMed, 38 citations in OpenAlex.
- Potential contributors to variable penetrance of NOTCH3 p.Arg1231Cys Variant.Neurogenetics · 2026Article
- Stratification by a polygenic risk score of common variation aids in Alzheimer's disease rare variant discovery.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Observational
- Epigenetic brain reprogramming rejuvenates neuro-immune circuits to reverse Alzheimer's disease pathology and systemic bone loss.Journal of neuroinflammation · 2026Article
- Comprehensive adjudication identifies 111 high-confidence loci for Alzheimer's disease and related dementias.medRxiv : the preprint server for health sciences · 2026Article
- Application of the STAAR framework in detecting rare variant associations with Alzheimer disease and related dementias: Insights and implications.HGG advances · 2026Article
- PLCG2 modulates TREM2 expression and signaling in response to Alzheimer's disease pathology.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Cell-type specific profiling of human entorhinal cortex at the onset of Alzheimer's disease neuropathology.bioRxiv : the preprint server for biology · 2025Article
- The Spectrum of Genetic Risk in Alzheimer Disease.Neurology. Genetics · 2025Review
- Non-coding variation in dementias: mechanisms, insights, and challenges.NPJ dementia · 2025Review
- Missense and loss-of-function variants at GWAS loci in familial Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Exploring first-degree family history in a cohort of Portuguese Alzheimer's disease patients: population evidence for X-chromosome linked and recessive inheritance of risk factors.Journal of neurology · 2024Article
- Serum proteomics reveal APOE-ε4-dependent and APOE-ε4-independent protein signatures in Alzheimer's disease.Nature aging · 2024Article
- In vivo validation of late-onset Alzheimer's disease genetic risk factors.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- The broken Alzheimer's disease genome.Cell genomics · 2024Review
- Emerging Role of ABC Transporters in Glia Cells in Health and Diseases of the Central Nervous System.Cells · 2024Review
- Serum proteomics reveals APOE dependent and independent protein signatures in Alzheimer's disease.Research square · 2024Article
- Neuroimaging techniques, gene therapy, and gut microbiota: frontier advances and integrated applications in Alzheimer's Disease research.Frontiers in aging neuroscience · 2024Review
- Article
- Serum proteomics revealsmedRxiv : the preprint server for health sciences · 2023Article
- Rejection of inappropriate synaptic partners in mouse retina mediated by transcellular FLRT2-UNC5 signaling.Developmental cell · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
The search for rare variants in Alzheimer's disease (AD) is usually deemed a high-risk - high-reward situation. The challenges associated with this endeavor are real. Still, the application of genome-wide technologies to large numbers of cases and controls or to small, well-characterized families has started to be fruitful.Rare variants associated with AD have been shown to increase risk or cause disease, but also to protect against the development of AD. All of these can potentially be targeted for the development of new drugs.Multiple independent studies have now shown associations of rare variants in NOTCH3, TREM2, SORL1, ABCA7, BIN1, CLU, NCK2, AKAP9, UNC5C, PLCG2, and ABI3 with AD and suggested that they may influence disease via multiple mechanisms. These genes have reported functions in the immune system, lipid metabolism, synaptic plasticity, and apoptosis. However, the main pathway emerging from the collective of genes harboring rare variants associated with AD is the Aβ pathway. Associations of rare variants in dozens of other genes have also been proposed, but have not yet been replicated in independent studies. Replication of this type of findings is one of the challenges associated with studying rare variants in complex diseases, such as AD. In this review, we discuss some of these primary challenges as well as possible solutions.Integrative approaches, the availability of large datasets and databases, and the development of new analytical methodologies will continue to produce new genes harboring rare variability impacting AD. In the future, more extensive and more diverse genetic studies, as well as studies of deeply characterized families, will enhance our understanding of disease pathogenesis and put us on the correct path for the development of successful drugs.
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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.