ArticleEuropean journal of human genetics : EJHG2015
Rare variants in β-Amyloid precursor protein (APP) and Parkinson's disease.
Article in European journal of human genetics : EJHG, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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32 citing papers in PubMed, 52 citations in OpenAlex.
- Mitochondrial Calcium Channels and MAM Interaction in Calcium Homeostasis Dysregulation in Parkinson's Disease.Neurochemical research · 2025Review
- Distinct spatial transcriptomic patterns of substantia Nigra in Parkinson disease and Parkinsonian subtype of multiple system atrophy.Acta neuropathologica communications · 2025Article
- Ferroptosis role in complexity of cell death: unrevealing mechanisms in Parkinson's disease and therapeutic approaches.Inflammopharmacology · 2025Review
- FTLD-MAPT mutations and short 5'UTR Tau mRNAs increase Tau translation.NAR molecular medicine · 2024Article
- Ubiquitin Carboxyl-Terminal Hydrolase L1 and Its Role in Parkinson's Disease.International journal of molecular sciences · 2024Review
- Double Mutations in a Patient with Early-Onset Alzheimer's Disease in Korea: AnInternational journal of molecular sciences · 2023Article
- Early-Onset Dementia-Parkinsonism with Rapid Development of Motor Fluctuations and Dyskinesia Due toMovement disorders clinical practice · 2023Article
- Unscrambling the Role of Redox-Active Biometals in Dopaminergic Neuronal Death and Promising Metal Chelation-Based Therapy for Parkinson's Disease.International journal of molecular sciences · 2023Review
- Study of molecular patterns associated with ferroptosis in Parkinson's disease and its immune signature.PloS one · 2023Article
- Rare Amyloid Precursor Protein Point Mutations Recapitulate Worldwide Migration and Admixture in Healthy Individuals: Implications for the Study of Neurodegeneration.International journal of molecular sciences · 2022Article
- Genetic landscape of early-onset dementia in Hungary.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2022Article
- A thermodynamic investigation of amyloid precursor protein processing by human γ-secretase.Communications biology · 2022Article
- Tau mRNA Metabolism in Neurodegenerative Diseases: A Tangle Journey.Biomedicines · 2022Review
- PGAGP: Predicting pathogenic genes based on adaptive network embedding algorithm.Frontiers in genetics · 2022Article
- Exome Sequencing of a Portuguese Cohort of Frontotemporal Dementia Patients: Looking Into the ALS-FTD Continuum.Frontiers in neurology · 2022Article
- Inflammatory seborrheic keratosis resolution after hyperbaric oxygen therapy: Case presentation and pathophysiology review.Dermatology reports · 2021Article
- Reduced erythrocytic CHCHD2 mRNA is associated with brain pathology of Parkinson's disease.Acta neuropathologica communications · 2021Article
- Genetic Pathways Involved in the Pathogenesis of Parkinson's Disease.Advances in experimental medicine and biology · 2021Article
- Central and Peripheral Metabolic Defects Contribute to the Pathogenesis of Alzheimer's Disease: Targeting Mitochondria for Diagnosis and Prevention.Antioxidants & redox signaling · 2020Review
- Targeting Tau to Treat Clinical Features of Huntington's Disease.Frontiers in neurology · 2020Review
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Authors and funding
27 authors at 11 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Many individuals with Parkinson's disease (PD) develop cognitive deficits, and a phenotypic and molecular overlap between neurodegenerative diseases exists. We investigated the contribution of rare variants in seven genes of known relevance to dementias (β-amyloid precursor protein (APP), PSEN1/2, MAPT (microtubule-associated protein tau), fused in sarcoma (FUS), granulin (GRN) and TAR DNA-binding protein 43 (TDP-43)) to PD and PD plus dementia (PD+D) in a discovery sample of 376 individuals with PD and followed by the genotyping of 25 out of the 27 identified variants with a minor allele frequency <5% in 975 individuals with PD, 93 cases with Lewy body disease on neuropathological examination, 613 individuals with Alzheimer's disease (AD), 182 cases with frontotemporal dementia and 1014 general population controls. Variants identified in APP were functionally followed up by Aβ mass spectrometry in transiently transfected HEK293 cells. PD+D cases harbored more rare variants across all the seven genes than PD individuals without dementia, and rare variants in APP were more common in PD cases overall than in either the AD cases or controls. When additional controls from publically available databases were added, one rare variant in APP (c.1795G>A(p.(E599K))) was significantly associated with the PD phenotype but was not found in either the PD cases or controls of an independent replication sample. One of the identified rare variants (c.2125G>A (p.(G709S))) shifted the Aβ spectrum from Aβ40 to Aβ39 and Aβ37. Although the precise mechanism remains to be elucidated, our data suggest a possible role for APP in modifying the PD phenotype as well as a general contribution of genetic factors to the development of dementia in individuals with PD.
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