Aug 2026· The journal of prevention of Alzheimer's disease· Vol 13· 0 citations· 56 references
Medicine
TL;DR
These findings link CP enlargement to neuropathologically confirmed AD burden and CI, supporting further investigation of CP structure and function in AD.
Abstract
Introduction The choroid plexus (CP) increases in volume across the Alzheimer’s disease (AD) continuum, suggesting its potential as a clearance-related biomarker. However, few studies have examined ante-mortem CP volume in relation to post-mortem AD pathology, the gold standard for diagnosis. Methods Participants who had structural magnetic resonance imaging and post-mortem pathology, with an interval of ≤ 5 years between imaging and death, were examined. Normalized CP volume (NCPV) was semi-automatically segmented from the lateral ventricles and analyzed using Bayesian linear regression to estimate associations with cognitive impairment (CI), AD pathology, and relevant clinical/demographic data. Results Intermediate and high levels of AD pathology and CI were associated with larger NCPV, whereas female sex was associated with lower NCPV. Subgroup analyses showed larger NCPV in individuals with greater CI despite comparable levels of AD pathology. Discussion These findings link CP enlargement to neuropathologically confirmed AD burden and CI, supporting further investigation of CP structure and function in AD.
Evidence supporting a causal relationship between CP morphological parameters and dementia risk that is partly mediated by specific brain phenotypes is provided, and it is suggested that the CP parameters may be valuable biomarkers for structural brain aging and dementia.
T. Yu, Xiaolei Han, Xin Huang et al.· Molecular Psychiatry· 0 citations
Background The comparative utility of choroid plexus volume (CPV) and the diffusion tensor imaging-based perivascular space (DTI-ALPS) index as glymphatic biomarkers across the Alzheimer’s disease (AD) continuum is unclear. This study aimed to perform a head-to-head comparison of their relationships with AD pathology, cognition, and diagnostic performance. Methods This study analyzed data from 848 AD Neuroimaging Initiative (ADNI) participants [426 cognitively normal (CN), 309 with mild cognitive impairment (MCI), and 113 with AD dementia]. Group differences in CPV and the ALPS index were assessed using generalized linear models (GLM), and their associations with AD biomarkers and cognition were examined via partial correlation. Diagnostic performance using logistic regression, and longitudinal predictive value was assessed with linear mixed models. Results Compared with the CN and MCI groups, patients with AD exhibited significantly increased CPV and reduced ALPS indices (all P<0.001). Amyloid-β-positive (Aβ+) participants also showed significantly higher CPV and lower ALPS indices than Aβ-negative (Aβ−) individuals (all P<0.001). Elevated CPV was associated with lower cerebrospinal fluid (CSF) Aβ42 (r=−0.15, P<0.001), poorer Mini-Mental State Examination (MMSE; r=−0.12, P<0.001), Montreal Cognitive Assessment (MoCA; r=−0.17, P<0.001), and reduced hippocampal volume (r=−0.21, P<0.001). Conversely, higher ALPS indices were associated with increased CSF Aβ42 (r=0.12, P<0.001), better MMSE (r=0.13, P<0.001), and preserved hippocampal volume (r=0.15, P<0.001). CPV achieved superior diagnostic performance for differentiating AD from MCI [area under the curve (AUC) =0.774] and CN (AUC =0.912). Moreover, integrating CPV, ALPS, and hippocampal volume further improved classification performance across diagnostic and Aβ stratification tasks. Longitudinal analyses demonstrated that higher baseline CPV was associated with better baseline cognitive performance and slower decline in executive, language, and memory functions, whereas lower baseline ALPS indices predicted accelerated memory decline over time. Conclusions Our findings identify CPV and the ALPS index as a pair of promising, complementary neuroimaging biomarkers for AD. Their synergistic integration into diagnostic models improves the precision of early detection and intervention strategies.
Mingyu Tan, Xiaosong Lan, Xiereniguli Anayiti et al.· Quantitative Imaging in Medi...· 0 citations
CP volume was increased in both active RMS and inactive PMS and was associated with lower total and cortical brain volumes, suggesting CP volume may reflect processes beyond MS-specific pathology, including physiological factors.
M. Mastantuono, A. Cagol, M. Ocampo-Pineda et al.· Multiple Sclerosis· 0 citations
ABSTRACT Objective Peak‐width of skeletonized mean diffusivity (PSMD) and diffusion tensor imaging–analysis along the perivascular space (DTI‐ALPS), reflecting white matter integrity and glymphatic function, are altered in Alzheimer's disease (AD). We evaluated whether these biomarkers differ between AD participants with and without concomitant cerebral amyloid angiopathy (CAA). Methods The study included 50 AD participants with mild cognitive impairment/mild dementia, and intermediate to high AD neuropathologic change at autopsy. AD was categorized as AD with CAA and AD without CAA based on CAA neuropathology. We evaluated global and regional (frontal, parietal, temporal and occipital) PSMD; left, right and mean DTI‐ALPS indices and their association with clinical measures [Clinical dementia rating sum‐of‐boxes (CDR‐SB) from CDR Dementia Staging Instrument, mini mental state examination (MMSE), cognitive composites: memory, processing speed, executive function, and language]. Results AD participants with CAA (n = 17) had higher global [4.02 ± 1.44 (mean ± SD × 10−4 mm2/s) vs. 3.12 ± 0.91, β = −0.80, 95% CI (−1.42, −0.18), p = 0.012] and occipital PSMD [4.02 ± 1.10 vs. 3.00 ± 1.08, β = −0.88, 95% CI (−1.51, −0.26), p = 0.026] than those without CAA. No PSMD metric was associated with any clinical measure. However, imaging‐by‐group interactions showed global PSMD associated with language [β = −0.89, 95% CI (−1.53, −0.26), p = 0.027] and parietal PSMD with language [β = −1.05, 95% CI (−1.74, −0.36), p = 0.014] and memory [β = −0.83, 95% CI (−1.38, −0.28), p = 0.015]. DTI‐ALPS indices did not differ by group. Higher mean and right DTI‐ALPS indices were associated with preserved language function [mean: β = 9.33, 95% CI (2.05, 16.62), p = 0.036; right: β = 7.75, 95% CI (1.54, 13.95), p = 0.043] without imaging‐by‐group interactions. Interpretation Global and occipital PSMD may help identify AD participants with concomitant CAA.
Debina Laishram, G. Du, Sangam Kanekar et al.· Annals of Clinical and Trans...· 0 citations
Standardized acquisition and segmentation, harmonized cognitive assessment, and adequately powered longitudinal studies are needed to establish their independent and predictive value for choroid plexus volume, as the evidence remains limited and methodologically heterogeneous.
Weronika Galus, Patrycja Romaniszyn-Kania, Aleksandra Urantówka et al.· Brain Science· 0 citations
Simple Summary Alzheimer’s disease progression involves complex changes in both the brain and the body, but the biological links between peripheral metabolic alterations and brain structural changes remain unclear. This study examined whether elevated blood homocysteine levels were associated with larger choroid plexus volume, an MRI-derived measure of the choroid plexus, a structure involved in maintaining the brain environment. In a large cohort covering normal cognition, mild cognitive impairment, and Alzheimer’s disease dementia, higher blood homocysteine levels were associated with increased choroid plexus volume, and larger choroid plexus volume was associated with a higher risk of progression from mild cognitive impairment to Alzheimer’s disease dementia. Exploratory reanalysis of independent postmortem single-nucleus and spatial transcriptomic datasets identified choroid plexus epithelial expression states involving one-carbon metabolism-related genes and spatial organization near vascular compartments. These independent transcriptomic findings provide tissue-level biological context for the associations observed in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and support further validation of these epithelial expression states.
Chenjie Feng, Tian Zhang, Xianglong Liu et al.· Biology· 0 citations
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