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

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

Large-scale cerebrospinal fluid proteomic analysis in Alzheimer’s disease patients reveals five molecular subtypes with distinct genetic risk profiles

“…On MRI, subtype 4 had the largest choroid plexus volume (figure 3b). Increased choroid plexus volume has been associated with inflammation and structural alterations by previous studies in AD [85][86][87] . Although this subtype most often had normal t-tau and p-tau levels (table 1), it had more severe atrophy in comparison to subtype 1, 3 and 5, and had specific atrophy in anterior cingulate areas (figure 3; S-figure 2).…”

An Association of Chitinase-3 Like-Protein-1 With Neuronal Deterioration in Multiple Sclerosis

“…In addition to the known role of CHI3L1 in neuroinflammation, this study highlights some previously unidentified roles of CHI3L1 in MS pathology, by identifying its association with neurodegeneration in GM and BBB abnormalities in the WM. These findings are further strengthened by the observed association of CHI3L1 positivity with the inflammation of the choroid plexus in the CPZ mouse (Supplementary Figure 2), since choroid plexus inflammation is correlated to neurodegeneration and malfunction of BBB (C ̌arna et al, 2023;Wolburg & Paulus, 2010).…”

The partial volume effect of choroid plexus in pathogenesis of Alzheimer's disease

“…For instance, gray matter and CSF volume fraction can be estimated using a T1-weighted image based on the combination of a novel hidden Markov random field (HMRF) and expectation-maximization (EM) (i.e., HMRF-EM) framework implemented in the FMRIB Software Library with the "FAST" command 3 and diffusion MRI utilizing free-water imaging, which can remove the effects of extracellular free water using an advanced free-water diffusion tensor model. 4 These approaches could improve the evidence level of the findings by Čarna et al, 1 and I hope this letter will contribute to reaching a final diagnosis in even more patients with clinical AD.…”

“…remodeling of ChP in AD, which is associated with aging and cognitive decline. 1 For the evaluation of ChP volumetry utilizing MRI, I would like to provide a few suggestions to better interpret these interesting results.…”