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Pathogenesis of Alzheimer's disease: Involvement of the choroid plexus. 2023
Maria Čarna, and
Isaac G Onyango, and
Stanislav Katina, and
Dušan Holub, and
Jan Sebastian Novotny, and
Marketa Nezvedova, and
Durga Jha, and
Zuzana Nedelska, and
Valentina Lacovich, and
Thijs Vande Vyvere, and
Ruben Houbrechts, and
Krystine Garcia-Mansfield, and
Ritin Sharma, and
Victoria David-Dirgo, and
Martin Vyhnalek, and
Kateřina Texlova, and
Hernan Chaves, and
Nadine Bakkar, and
Lucia Pertierra, and
Mojmir Vinkler, and
Hana Markova, and
Jan Laczo, and
Kateřina Sheardova, and
Marcela Hortova-Kohoutkova, and
Jan Frič, and
Giancarlo Forte, and
Petr Kaňovsky, and
Silvie Belaškova, and
Jiři Damborsky, and
Jakub Hort, and
Nicholas T Seyfried, and
Robert Bowser, and
Gustavo Sevlever, and
Robert A Rissman, and
Richard A Smith, and
Marian Hajduch, and
Patrick Pirrotte, and
Zdenek Spacil, and
Eric B Dammer, and
Clara Limbäck-Stokin, and
Gorazd B Stokin
International Clinical Research Centre, St. Anne's University Hospital, Brno, Czech Republic.
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.
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