Year: 2021
Type: preprint
Study design: Observational Study
Abstract: Summary Aging and Alzheimer’s disease (AD), a major age-related disorder, are both characterized by inflammatory changes in the cerebrospinal fluid (CSF). The origin and the mechanisms underlying these inflammatory changes, however, remain poorly understood. Here, we report that aging elicits inflammatory changes in the CSF that become accentuated uniquely in AD compared to other inflammatory and neurodegenerative disorders. We show that the choroid plexus (ChP), which produces CSF, gains a pro-inflammatory profile, exhibits perturbed metabolism and contributes to the CSF changes observed in AD. We then use MRI imaging to establish a correlation between cognitive decline and increased volume of significantly remodelled ChP in patients with AD, and provide clinical relevance to the identified ChP pathology. These findings collectively suggest that ChP, unable to resolve inflammatory insults efficiently over the lifetime, participates in the inflammation and the pathogenesis of AD.
Source: medRxiv
Authors: Maria Čarna, Isaac G. Onyango, Stanislav Katina, Dušan Holub, Marketa Nezvedova, Durga Jha, Zuzana Nedelska, Valentina Lacovich, Thijs Vande Vyvere, Ruben Houbrechts, Krystine Garcia-Mansfield, Ritin Sharma, Victoria David-Dirgo, Martin Vyhnalek, Kateřina Texlova, Hernan Chaves, Nadine Bakkar, Lucia Pertierra, Mojmir Vinkler, Hana Markova, Jan Laczo, Kateřina Sheardova, Jan Frič, Antonio Pompeano, Giancarlo Forte, Petr Kaňovsky, Silvie Belaškova, Jiři Damborsky, Jakub Hort, Nicholas T. Seyfried, Robert Bowser, Gustavo Sevlever, Robert A. Rissman, Richard A. Smith, Marian Hajduch, Patrick Pirrotte, Zdeněk Spačil, Eric B. Dammer, Clara Limbäck-Stokin, Gorazd B. Stokin
Institutions: International Clinical Research Center, St. Anne's University Hospital Brno, St. Anne's University Hospital Brno, Masaryk University, Institute of Molecular and Translational Medicine, Palacký University Olomouc, RECETOX, Charles University, University Hospital in Motol, Icometrix (Belgium), Translational Genomics Research Institute, Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia, Barrow Neurological Institute, Institute of Haematology and Blood Transfusion, University Hospital Olomouc, Emory University, University of California San Diego, Center for Neurologic Study, City Of Hope National Medical Center, City of Hope, Imperial College Healthcare NHS Trust, Imperial College London, Mayo Clinic, Ljubljana University Medical Centre
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
Funders: Alzheimer's Disease Neuroimaging Initiative, Barrow Neurological Foundation, Target ALS, Parkinson's UK, Imperial College London, Ministerstvo Školství, Mládeže a Tělovýchovy, Masarykova Univerzita, National Institutes of Health, University of California, San Diego, RECETOX Přírodovědecké Fakulty Masarykovy Univerzity, National Institute on Aging, National Cancer Institute
Awards: G1059663884, G1065084423, G1067330246, G19608704, G2020983025, G2706813561, G2736700079, G3051306476, G3120673997, G3275786764, RECETOX RI, G3535654666, National institute for Neurological Research, G3725267068, G4113699340, G4635590560, G5124248554, G5641063287, G6407950216, G7710866549, G772794905, G7802814758, G874294283, G882351932, G9000092632, G9000170943, G9000260180
OpenAlex ID: W3189257569