Pathogenesis of Alzheimer's disease: Involvement of the choroid plexus
Mária Čarná, Isaac G. Onyango, Stanislav Katina, Dušan Holub, Jan Novotný, Markéta Nezvedová, Durga Jha, Zuzana Nedelská, Valentina Lacovich, Thijs Vande Vyvere, Ruben Houbrechts, Krystine Garcia‐Mansfield, Ritin Sharma, Victoria David‐Dirgo, Martin Vyhnálek, Kateřina Texlova, Hernán Chaves, Nadine Bakkar, Lucía Pertierra, Mojmír Vinkler, Hana Marková, Jan Laczó, Kateřina Sheardová, Marcela Hortová Kohoutková, Jan Frič, Giancarlo Forte, Petr Kaňovský, Silvie Bělašková, Jiřı́ Damborský, Jakub Hort, Nicholas T. Seyfried, Robert Bowser, Gustavo Sevlever, Robert A. Rissman, Richard Smith, Marián Hajdúch, Patrick Pirrotte, Zdeněk Spáčil, Eric B. Dammer, Clara Limbäck‐Stokin, Gorazd B. Stokin
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.