Perivascular spaces are associated with tau pathophysiology and synaptic dysfunction in early Alzheimer’s continuum
Autor: | Maria Emilio, Sandra Pradas, Annabella Beteta, Albina Polo, Tania Menchon, Henrik Zetterberg, Gemma Salvadó, Gema Huesa, Natalia Vilor-Tejedor, Kaj Blennow, Roderic Guigó, Juan Domingo Gispert, Marc Suárez-Calvet, Karine Fauria, Mahnaz Shekari, Anna Brugulat, Gwendlyn Kollmorgen, Laura Hernandez, Alba Cañas, Ruth Dominguez, Carme Deulofeu, Iacopo Ciampa, José Luis Molinuevo, Paula Marne, Marta Milà-Alomà, Sherezade Fuentes, Marta Crous-Bou, Carles Falcon, Aleix Sala-Vila, Grégory Operto, Blanca Rodriguez-fernandez, Jordi Huguet, Anna Soteras, Irene Cumplido, Oriol Grau-Rivera, Gonzalo Sánchez-Benavides, Raffaele Cacciaglia, Marc Vilanova, Eider M. Arenaza-Urquijo, Carolina Minguillon |
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Přispěvatelé: | Clinical Genetics |
Rok vydání: | 2021 |
Předmět: |
Cognitive Neuroscience
Perivascular spaces Library science tau Proteins Neurosciences. Biological psychiatry. Neuropsychiatry Virchow-Robin spaces Basal Ganglia 03 medical and health sciences 0302 clinical medicine Alzheimer Disease Political science Agency (sociology) Humans media_common.cataloged_instance Receptors Immunologic European union RC346-429 CSF biomarkers 030304 developmental biology media_common 0303 health sciences Government Amyloid beta-Peptides Membrane Glycoproteins Research Líquid cefalorraquidi Middle Aged Alzheimer's disease Magnetic Resonance Imaging language.human_language 3. Good health Malaltia d'Alzheimer Cerebrospinal fluid Neurology General partnership alpha-Synuclein language Catalan Neurology. Diseases of the nervous system Neurology (clinical) Tau pathophysiology Alzheimer’s disease Biomarkers 030217 neurology & neurosurgery MRI RC321-571 Swedish government Dementia research Health department |
Zdroj: | Dipòsit Digital de la UB Universidad de Barcelona Alzheimer's Research and Therapy, 13(1):135. BioMed Central Ltd. Alzheimer’s Research & Therapy, Vol 13, Iss 1, Pp 1-13 (2021) Alzheimer's Research & Therapy |
ISSN: | 1758-9193 |
Popis: | Background: Perivascular spaces (PVS) have an important role in the elimination of metabolic waste from the brain. It has been hypothesized that the enlargement of PVS (ePVS) could be affected by pathophysiological mechanisms involved in Alzheimer's disease (AD), such as abnormal levels of CSF biomarkers. However, the relationship between ePVS and these pathophysiological mechanisms remains unknown. Objective: We aimed to investigate the association between ePVS and CSF biomarkers of several pathophysiological mechanisms for AD. We hypothesized that ePVS will be associated to CSF biomarkers early in the AD continuum (i.e., amyloid positive cognitively unimpaired individuals). Besides, we explored associations between ePVS and demographic and cardiovascular risk factors. Methods: The study included 322 middle-aged cognitively unimpaired participants from the ALFA + study, many within the Alzheimer's continuum. NeuroToolKit and Elecsys® immunoassays were used to measure CSF Aβ42, Aβ40, p-tau and t-tau, NfL, neurogranin, TREM2, YKL40, GFAP, IL6, S100, and α-synuclein. PVS in the basal ganglia (BG) and centrum semiovale (CS) were assessed based on a validated 4-point visual rating scale. Odds ratios were calculated for associations of cardiovascular and AD risk factors with ePVS using logistic and multinomial models adjusted for relevant confounders. Models were stratified by Aβ status (positivity defined as Aβ42/40 < 0.071). Results: The degree of PVS significantly increased with age in both, BG and CS regions independently of cardiovascular risk factors. Higher levels of p-tau, t-tau, and neurogranin were significantly associated with ePVS in the CS of Aβ positive individuals, after accounting for relevant confounders. No associations were detected in the BG neither in Aβ negative participants. Conclusions: Our results support that ePVS in the CS are specifically associated with tau pathophysiology, neurodegeneration, and synaptic dysfunction in asymptomatic stages of the Alzheimer's continuum. The project leading to these results has received funding from “la Caixa” Foundation (ID 100010434), under agreement LCF/PR/GN17/50300004 and the Alzheimer’s Association and an international anonymous charity foundation through the TriBEKa Imaging Platform project (TriBEKa-17–519007). Additional support has been received from the Health Department of the Catalan Government (Health Research and Innovation Strategic Plan (PERIS) 2016–2020 grant# SLT002/16/00201) and the Universities and Research Secretariat, Ministry of Business and Knowledge of the Catalan Government under the grant no. 2017-SGR-892. All CRG authors acknowledge the support of the Spanish Ministry of Science, Innovation and Universities to the EMBL partnership, the Centro de Excelencia Severo Ochoa, and the CERCA Programme/Generalitat de Catalunya. NV-T is funded by a post-doctoral grant, Juan de la Cierva Programme (FJC2018-038085-I), Ministry of Science and Innovation– Spanish State Research Agency. MS-C received funding from the European Union’s Horizon 2020 Research and Innovation Program under the Marie Sklodowska-Curie action grant agreement No 752310, and currently receives funding from Instituto de Salud Carlos III (PI19/00155) and from the Spanish Ministry of Science, Innovation and Universities (Juan de la Cierva Programme grant IJC2018-037478-I). EMAU is supported by the Spanish Ministry of Science, Innovation and Universities—Spanish State Research Agency (RYC2018-026053-I). OGR is supported by the Spanish Ministry of Science, Innovation and Universities (FJCI-2017–33437). JDG is supported by the Spanish Ministry of Science and Innovation (RYC-2013–13054). KB is supported by the Swedish Research Council (#2017–00915), the Alzheimer Drug Discovery Foundation (ADDF), USA (#RDAPB-201809–2016615), the Swedish Alzheimer Foundation (#AF-742881), Hjärnfonden, Sweden (#FO2017-0243), the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (#ALFGBG-715986), and European Union Joint Program for Neurodegenerative Disorders (JPND2019-466–236). HZ is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018–02532), the European Research Council (#681712), the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (#ALFGBG-720931), the ADDF, USA (#201809–2016862), and the UK Dementia Research Institute at UCL. |
Databáze: | OpenAIRE |
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