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.

1st Department of Neurology St Anne's University Hospital and Faculty of Medicine Masaryk University Brno Czech Republic

Center for Neurodegenerative Disease Emory University School of Medicine Atlanta Georgia USA

Center for Neurologic Study La Jolla California USA

Collaborative Center for Translational Mass Spectrometry Translational Genomics Research Institute Phoenix Arizona USA

Department of Cellular Pathology Imperial College Healthcare NHS Trust London UK

Department of Neurobiology Barrow Neurological Institute Phoenix Arizona USA

Department of Neurology Faculty of Medicine and Dentistry Palacky University Olomouc and Research and Science Department University Hospital Olomouc Olomouc Czech Republic

Department of Neurosciences University of California San Diego La Jolla California USA

Departments of Bioachemistry and Neurology Emory University School of Medicine Atlanta Georgia USA

Division of Neurology University Medical Centre Ljubljana Slovenia

FLENI Buenos Aires Argentina

Goizueta Alzheimer's Disease Research Center Emory University Atlanta Georgia USA

Icometrix Leuven Belgium

Imperial College London Faculty of Medicine London UK

Institute for Molecular and Translational Medicine Faculty of Medicine and Dentistry Palacky University Olomouc Olomouc Czech Republic

Institute of Hematology and Blood Transfusion Prague Czech Republic

Institute of Mathematics and Statistics Masaryk University Brno Czech Republic

International Clinical Research Centre St Anne's University Hospital Brno Czech Republic

Mass Spectrometry and Proteomics Core Facility City of Hope Comprehensive Cancer Center Duarte California USA

Memory Clinic Department of Neurology 2nd Faculty of Medicine Charles University and Motol University Hospital Prague Czech Republic

RECETOX Centre Faculty of Sciences Masaryk University Brno Czech Republic

Translational Aging and Neuroscience Program Mayo Clinic Rochester Minnesota USA

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Longitudinal progression of choroid plexus enlargement is associated with female sex, cognitive decline and ApoE E4 homozygote status