ArticleActa neuropathologica communications2022
Rare missense mutations in ABCA7 might increase Alzheimer's disease risk by plasma membrane exclusion.
Article in Acta neuropathologica communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 22 citations in OpenAlex.
- Advancements in the Study of Missense Mutations in ABCA7 in Alzheimer's Disease.Journal of molecular neuroscience : MN · 2026Review
- The impact of rare genetic variants on Alzheimer disease.Nature reviews. Neurology · 2025Review
- Neuronal ABCA7 deficiency aggravates mitochondrial dysfunction and neurodegeneration in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Haploinsufficiency and Alzheimer's Disease: The Possible Pathogenic and Protective Genetic Factors.International journal of molecular sciences · 2024Review
- Identification ofAnimal biotechnology · 2024Article
- AlzDiscovery: A computational tool to identify Alzheimer's disease-causing missense mutations using protein structure information.Protein science : a publication of the Protein Society · 2024Article
- The Abca7Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- The ABC's of Alzheimer risk gene ABCA7.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Review
- Emerging Role of ABC Transporters in Glia Cells in Health and Diseases of the Central Nervous System.Cells · 2024Review
- Patient with PSEN1 Glu318Gly and Other Possible Disease Risk Mutations, Diagnosed with Early Onset Alzheimer's Disease.International journal of molecular sciences · 2023Article
- Clinical considerations in early-onset cerebral amyloid angiopathy.Brain : a journal of neurology · 2023Review
- ABCA7-Associated Clinical Features and Molecular Mechanisms in Alzheimer's Disease.Molecular neurobiology · 2023Review
- Genetic Phenotypes of Alzheimer's Disease: Mechanisms and Potential Therapy.Phenomics (Cham, Switzerland) · 2023Review
- PSEN2 and ABCA7 variants causing early-onset preclinical pathological changes in Alzheimer's disease: a case report and literature review.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2023Review
- Emerging Alzheimer's disease therapeutics: promising insights from lipid metabolism and microglia-focused interventions.Frontiers in aging neuroscience · 2023Review
- The role of ATP-binding cassette subfamily A in the etiology of Alzheimer's disease.Molecular neurodegeneration · 2022Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The adenosine triphosphate-binding cassette subfamily A member 7 gene (ABCA7) is associated with Alzheimer's disease (AD) in large genome-wide association studies. Targeted sequencing of ABCA7 suggests a role for rare premature termination codon (PTC) mutations in AD, with haploinsufficiency through nonsense-mediated mRNA decay as a plausible pathogenic mechanism. Since other classes of rare variants in ABCA7 are poorly understood, we investigated the contribution and pathogenicity of rare missense, indel and splice variants in ABCA7 in Belgian AD patient and control cohorts. We identified 8.36% rare variants in the patient cohort versus 6.05% in the control cohort. For 10 missense mutations identified in the Belgian cohort we analyzed the pathogenetic effect on protein localization in vitro using immunocytochemistry. Our results demonstrate that rare ABCA7 missense mutations can contribute to AD by inducing protein mislocalization, resulting in a lack of functional protein at the plasma membrane. In one pedigree, a mislocalization-inducing missense mutation in ABCA7 (p.G1820S) co-segregated with AD in an autosomal dominant inheritance pattern. Brain autopsy of six patient missense mutation carriers showed typical AD neuropathological characteristics including cerebral amyloid angiopathy type 1. Also, among the rare ABCA7 missense mutations, we observed mutations that affect amino acid residues that are conserved in ABCA1 and ABCA4, of which some correspond to established ABCA1 or ABCA4 disease-causing mutations involved in Tangier or Stargardt disease.
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