Relationship of cognitive decline with glucocerebrosidase activity and amyloid-beta 42 in DLB and PD.
| Title: | Relationship of cognitive decline with glucocerebrosidase activity and amyloid-beta 42 in DLB and PD. |
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| Authors: | Gonzalez MC; Department of Quality and Health Technology, Faculty of Health Sciences, University of Stavanger, Stavanger, Norway.; Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway.; Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway.; Oftedal L; Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway.; Lange J; Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway.; Department of Chemistry, Bioscience and Environmental Engineering, University of Stavanger, Stavanger, Norway.; Tovar-Rios DA; Department of Quality and Health Technology, Faculty of Health Sciences, University of Stavanger, Stavanger, Norway.; Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway.; Tysnes OB; Department of Neurology, Haukeland University Hospital, Bergen, Norway.; Paquet C; Neurology Center, Assistance Publique Hôpitaux de Paris, Lariboisière Fernand-Widal Hospital, INSERMU1144, Université de Paris, Paris, France.; Marquié M; Ace Alzheimer Center Barcelona-Universitat Internacional de Catalunya, Barcelona, Spain.; CIBERNED, Center for Networked Biomedical Research On Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain.; Boada M; Ace Alzheimer Center Barcelona-Universitat Internacional de Catalunya, Barcelona, Spain.; CIBERNED, Center for Networked Biomedical Research On Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain.; Alcolea D; Sant Pau Memory Unit, Department of Neurology, IIB Sant Pau-Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.; Rejdak K; Department of Neurology, Medical University of Lublin, Lublin, Poland.; Papuc E; Department of Neurology, Medical University of Lublin, Lublin, Poland.; Hort J; Department of Neurology, Memory Clinic, Charles University, Second Faculty of Medicine and Motol University Hospital, Prague, Czech Republic.; Falup-Pecurariu C; Department of Neurology, County Clinic Hospital, Faculty of Medicine, Transilvania University, Brasov, Romania.; Aarsland D; Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway.; Department of Psychological Medicine Institute of Psychiatry, Psychology & Neuroscience King's College London, London, UK.; Alves G; Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway.; Departement of Neurology, Stavanger University Hospital, Stavanger, Norway.; Maple-Grødem J; Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway.; Department of Chemistry, Bioscience and Environmental Engineering, University of Stavanger, Stavanger, Norway. |
| Source: | Annals of clinical and translational neurology [Ann Clin Transl Neurol] 2025 May; Vol. 12 (5), pp. 915-924. Date of Electronic Publication: 2025 Mar 06. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Wiley Periodicals, Inc on behalf of American Neurological Association Country of Publication: United States NLM ID: 101623278 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2328-9503 (Electronic) Linking ISSN: 23289503 NLM ISO Abbreviation: Ann Clin Transl Neurol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [Hoboken, NJ] : Wiley Periodicals, Inc on behalf of American Neurological Association, [2014]- |
| MeSH Terms: | Glucosylceramidase*/genetics ; Glucosylceramidase*/metabolism ; Glucosylceramidase*/cerebrospinal fluid ; Amyloid beta-Peptides*/cerebrospinal fluid ; Parkinson Disease*/cerebrospinal fluid ; Parkinson Disease*/genetics ; Parkinson Disease*/complications ; Cognitive Dysfunction*/cerebrospinal fluid ; Cognitive Dysfunction*/genetics ; Cognitive Dysfunction*/etiology ; Peptide Fragments*/cerebrospinal fluid ; Lewy Body Disease*/cerebrospinal fluid ; Lewy Body Disease*/genetics ; Lewy Body Disease*/complications; Biomarkers/cerebrospinal fluid ; Humans ; Male ; Female ; Aged ; Middle Aged ; Aged, 80 and over |
| Abstract: | Objective: Dementia with Lewy bodies (DLB) and Parkinson's disease (PD) share clinical, pathological, and genetic risk factors, including GBA1 and APOEε4 mutations. Biomarkers associated with the pathways of these mutations, such as glucocerebrosidase enzyme (GCase) activity and amyloid-beta 42 (Aβ42) levels, may hold potential as predictive indicators, providing valuable insights into the likelihood of cognitive decline within these diagnoses. Our objective was to determine their association with cognitive decline in DLB and PD.; Methods: A total of 121 DLB patients from the European-DLB Consortium and 117 PD patients from the Norwegian ParkWest Study were included in this study. The four most commonly associated variants of GBA1 mutations (E326K, T369M, N370S, L444P), APOEε4 status, and cerebrospinal fluid (CSF) Aβ42 levels and GCase activity were assessed, as well as global cognition using the Mini-Mental State Examination. Linear mixed-effects regression models were used to evaluate the association of CSF biomarkers with cognitive decline in each diagnostic group, adjusted for age, sex, education, and genetic mutation profile.; Results: Low CSF Aβ42 levels were associated with accelerated cognitive decline in DLB, whereas reduced CSF GCase activity predicted faster cognitive decline in PD. These associations were independent of GBA1 gene mutations or APOEε4 status.; Interpretation: Our study provides important evidence on the relationship between brain Aβ deposition and GCase activity in the Lewy body disease spectrum independent of their genetic mutation profile. This information could be relevant for designing future clinical trials targeting these pathways.; (© 2025 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.) |
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| Grant Information: | 911218 Western Norway Regional Health Authority; 911949 Western Norway Regional Health Authority; PI18/00435 Instituto de Salud Carlos III; PI22/00611 Instituto de Salud Carlos III; INT19/00016 Instituto de Salud Carlos III; INT23/00048 Instituto de Salud Carlos III; 177966 Research Council of Norway; PERIS program SLT006/17/125 Departament de Salut, Generalitat de Catalunya; LX22NPO5107 MEYS Next Generation EU |
| Substance Nomenclature: | EC 3.2.1.45 (Glucosylceramidase); 0 (Amyloid beta-Peptides); 0 (amyloid beta-protein (1-42)); 0 (Peptide Fragments); 0 (Biomarkers); EC 3.2.1.45 (GBA protein, human) |
| Entry Date(s): | Date Created: 20250307 Date Completed: 20250521 Latest Revision: 20250523 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC12093344 |
| DOI: | 10.1002/acn3.52295 |
| PMID: | 40051075 |
| Database: | MEDLINE |
Journal Article