SynthesisActa neuropathologica2014
ABCC9 gene polymorphism is associated with hippocampal sclerosis of aging pathology.
Synthesis in Acta neuropathologica, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 2 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.
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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.
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Who cites it
74 citing papers in PubMed, 2 syntheses or guidelines pooled it, 91 citations in OpenAlex.
- Genome wide association study meta-analysis of neuropathologic lesions of Alzheimer's disease and related dementias in a multi-site autopsy cohort.PLoS genetics · 2026Pooled it
- Dissecting Complex and Multifactorial Nature of Alzheimer's Disease Pathogenesis: a Clinical, Genomic, and Systems Biology Perspective.Molecular neurobiology · 2016Pooled it
- Article
- ABCC9/SUR2 has a Complex Expression Pattern in Human Brain Gliovascular Unit Cells, Including Astrocytes.Journal of molecular neuroscience : MN · 2026Article
- Cognitive Decline, Neurologic Involvement, and Neonatal Crisis inNeurology. Genetics · 2026Article
- Heterogeneity characterization and key pathogenic genes screening based on diabetic nephropathy microenvironment.Open life sciences · 2026Article
- The mechanisms underlying TDP-43-associated neurodegeneration in Alzheimer's disease and related dementias.Molecular psychiatry · 2025Review
- Nicorandil treatment improves survival and spatial learning in aged granulin knockout mice.Brain pathology (Zurich, Switzerland) · 2025Article
- Celebrating 40 years of the University of Kentucky Alzheimer's Disease Research Center.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- The Nun Study: Insights from 30 years of aging and dementia research.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Molecular pathogenesis of Alzheimer's disease onset in a mouse model: effects of cannabidiol treatment.Frontiers in neuroscience · 2025Article
- Polygenic associations with clinical and neuropathological trait heterogeneity across TDP-43 proteinopathies.PloS one · 2025Article
- Deep joint learning diagnosis of Alzheimer's disease based on multimodal feature fusion.BioData mining · 2024Article
- GWAS of multiple neuropathology endophenotypes identifies new risk loci and provides insights into the genetic risk of dementia.Nature genetics · 2024Article
- Limbic-predominant age-related TDP-43 encephalopathy (LATE-NC): Co-pathologies and genetic risk factors provide clues about pathogenesis.Journal of neuropathology and experimental neurology · 2024Review
- Novel loss-of-function variants expand ABCC9-related intellectual disability and myopathy syndrome.Brain : a journal of neurology · 2024Article
- Association of TMEM106B with CorticalGenes · 2024Article
- Genetic associations with age at dementia onset in the PSEN1 E280A Colombian kindred.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Article
- Limbic-predominant age-related TDP43 encephalopathy (LATE) neuropathological change in neurodegenerative diseases.Nature reviews. Neurology · 2023Review
- LATE-NC risk alleles (in TMEM106B, GRN, and ABCC9 genes) among persons with African ancestry.Journal of neuropathology and experimental neurology · 2023Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
47 authors at 15 institutions in 1 country.
Funding
Abstract
Hippocampal sclerosis of aging (HS-Aging) is a high-morbidity brain disease in the elderly but risk factors are largely unknown. We report the first genome-wide association study (GWAS) with HS-Aging pathology as an endophenotype. In collaboration with the Alzheimer's Disease Genetics Consortium, data were analyzed from large autopsy cohorts: (#1) National Alzheimer's Coordinating Center (NACC); (#2) Rush University Religious Orders Study and Memory and Aging Project; (#3) Group Health Research Institute Adult Changes in Thought study; (#4) University of California at Irvine 90+ Study; and (#5) University of Kentucky Alzheimer's Disease Center. Altogether, 363 HS-Aging cases and 2,303 controls, all pathologically confirmed, provided statistical power to test for risk alleles with large effect size. A two-tier study design included GWAS from cohorts #1-3 (Stage I) to identify promising SNP candidates, followed by focused evaluation of particular SNPs in cohorts #4-5 (Stage II). Polymorphism in the ATP-binding cassette, sub-family C member 9 (ABCC9) gene, also known as sulfonylurea receptor 2, was associated with HS-Aging pathology. In the meta-analyzed Stage I GWAS, ABCC9 polymorphisms yielded the lowest p values, and factoring in the Stage II results, the meta-analyzed risk SNP (rs704178:G) attained genome-wide statistical significance (p = 1.4 × 10(-9)), with odds ratio (OR) of 2.13 (recessive mode of inheritance). For SNPs previously linked to hippocampal sclerosis, meta-analyses of Stage I results show OR = 1.16 for rs5848 (GRN) and OR = 1.22 rs1990622 (TMEM106B), with the risk alleles as previously described. Sulfonylureas, a widely prescribed drug class used to treat diabetes, also modify human ABCC9 protein function. A subsample of patients from the NACC database (n = 624) were identified who were older than age 85 at death with known drug history. Controlling for important confounders such as diabetes itself, exposure to a sulfonylurea drug was associated with risk for HS-Aging pathology (p = 0.03). Thus, we describe a novel and targetable dementia risk factor.
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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.