Pathogenesis of Alzheimer's disease: Involvement of the choroid plexus

Maria Čarna, International Clinical Research Centre, St. Anne's University Hospital, Brno, Czech Republic.
Isaac G. Onyango, International Clinical Research Centre, St. Anne's University Hospital, Brno, Czech Republic.
Stanislav Katina, International Clinical Research Centre, St. Anne's University Hospital, Brno, Czech Republic.
Dušan Holub, Institute for Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic.
Jan Sebastian Novotny, International Clinical Research Centre, St. Anne's University Hospital, Brno, Czech Republic.
Marketa Nezvedova, RECETOX Centre, Faculty of Sciences, Masaryk University, Brno, Czech Republic.
Durga Jha, RECETOX Centre, Faculty of Sciences, Masaryk University, Brno, Czech Republic.
Zuzana Nedelska, International Clinical Research Centre, St. Anne's University Hospital, Brno, Czech Republic.
Valentina Lacovich, International Clinical Research Centre, St. Anne's University Hospital, Brno, Czech Republic.
Thijs Vande Vyvere, Icometrix, Leuven, Belgium.
Ruben Houbrechts, Icometrix, Leuven, Belgium.
Krystine Garcia-Mansfield, Collaborative Center for Translational Mass Spectrometry, Translational Genomics Research Institute, Phoenix, Arizona, USA.
Ritin Sharma, Collaborative Center for Translational Mass Spectrometry, Translational Genomics Research Institute, Phoenix, Arizona, USA.
Victoria David-Dirgo, Collaborative Center for Translational Mass Spectrometry, Translational Genomics Research Institute, Phoenix, Arizona, USA.
Martin Vyhnalek, International Clinical Research Centre, St. Anne's University Hospital, Brno, Czech Republic.
Kateřina Texlova, International Clinical Research Centre, St. Anne's University Hospital, Brno, Czech Republic.
Hernan Chaves, FLENI, Buenos Aires, Argentina.
Nadine Bakkar, Department of Neurobiology, Barrow Neurological Institute, Phoenix, Arizona, USA.Follow
Lucia Pertierra, FLENI, Buenos Aires, Argentina.
Mojmir Vinkler, Institute of Mathematics and Statistics, Masaryk University, Brno, Czech Republic.
Hana Markova, International Clinical Research Centre, St. Anne's University Hospital, Brno, Czech Republic.
Jan Laczo, International Clinical Research Centre, St. Anne's University Hospital, Brno, Czech Republic.
Kateřina Sheardova, International Clinical Research Centre, St. Anne's University Hospital, Brno, Czech Republic.
Marcela Hortova-Kohoutkova, International Clinical Research Centre, St. Anne's University Hospital, Brno, Czech Republic.
Jan Frič, International Clinical Research Centre, St. Anne's University Hospital, Brno, Czech Republic.
Giancarlo Forte, International Clinical Research Centre, St. Anne's University Hospital, Brno, Czech Republic.
Petr Kaňovsky, Department of Neurology, Faculty of Medicine and Dentistry, Palacky University Olomouc and Research and Science Department, University Hospital Olomouc, Olomouc, Czech Republic.
Silvie Belaškova, International Clinical Research Centre, St. Anne's University Hospital, Brno, Czech Republic.
Jiři Damborsky, International Clinical Research Centre, St. Anne's University Hospital, Brno, Czech Republic.
Jakub Hort, International Clinical Research Centre, St. Anne's University Hospital, Brno, Czech Republic.
Nicholas T. Seyfried, Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, Georgia, USA.
Robert Bowser, Department of Neurobiology, Barrow Neurological Institute, Phoenix, Arizona, USA.Follow

Document Type

Article

Abstract

The choroid plexus (ChP) produces and is bathed in the cerebrospinal fluid (CSF), which in aging and Alzheimer's disease (AD) shows extensive proteomic alterations including evidence of inflammation. Considering inflammation hampers functions of the involved tissues, the CSF abnormalities reported in these conditions are suggestive of ChP injury. Indeed, several studies document ChP damage in aging and AD, which nevertheless remains to be systematically characterized. We here report that the changes elicited in the CSF by AD are consistent with a perturbed aging process and accompanied by aberrant accumulation of inflammatory signals and metabolically active proteins in the ChP. Magnetic resonance imaging (MRI) imaging shows that these molecular aberrancies correspond to significant remodeling of ChP in AD, which correlates with aging and cognitive decline. Collectively, our preliminary post-mortem and in vivo findings reveal a repertoire of ChP pathologies indicative of its dysfunction and involvement in the pathogenesis of AD. HIGHLIGHTS: Cerebrospinal fluid changes associated with aging are perturbed in Alzheimer's disease Paradoxically, in Alzheimer's disease, the choroid plexus exhibits increased cytokine levels without evidence of inflammatory activation or infiltrates In Alzheimer's disease, increased choroid plexus volumes correlate with age and cognitive performance.

Keywords

Alzheimer's disease, aging, cerebrospinal fluid, choroid plexus, pathology

Publication Date

2-24-2023

Publication Title

Alzheimer's & dementia : the journal of the Alzheimer's Association

E-ISSN

1552-5279

PubMed ID

36825691

Digital Object Identifier (DOI)

10.1002/alz.12970

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