Association of Plasma Markers of Alzheimer's Disease, Neurodegeneration, and Neuroinflammation with the Choroid Plexus Integrity in Aging

Mustapha Bouhrara; Keenan A Walker; Joseph S R Alisch; Zhaoyuan Gong; Caio H Mazucanti; Alexandria Lewis; Abhay R Moghekar; Lisa Turek; Victoria Collingham; Nader Shehadeh; Giovanna Fantoni; Mary Kaileh; Christopher M Bergeron; Jan Bergeron; Susan M Resnick; Josephine M Egan

doi:10.14336/AD.2023.1226

Association of Plasma Markers of Alzheimer's Disease, Neurodegeneration, and Neuroinflammation with the Choroid Plexus Integrity in Aging

Aging Dis. 2024 Jan 8. doi: 10.14336/AD.2023.1226. Online ahead of print.

Authors

Mustapha Bouhrara¹, Keenan A Walker², Joseph S R Alisch¹, Zhaoyuan Gong¹, Caio H Mazucanti¹, Alexandria Lewis³, Abhay R Moghekar³, Lisa Turek⁴, Victoria Collingham⁴, Nader Shehadeh⁴, Giovanna Fantoni⁴, Mary Kaileh⁴, Christopher M Bergeron¹, Jan Bergeron¹, Susan M Resnick², Josephine M Egan¹

Affiliations

¹ Laboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
² Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
³ Johns Hopkins University School of Medicine, Baltimore, 21224 MD, USA.
⁴ Clinical Research Core, Baltimore, MD 21224, USA.

PMID: 38300640
DOI: 10.14336/AD.2023.1226

Abstract

The choroid plexus (CP) is a vital brain structure essential for cerebrospinal fluid (CSF) production. Moreover, alterations in the CP's structure and function are implicated in molecular conditions and neuropathologies including multiple sclerosis, Alzheimer's disease, and stroke. Our goal is to provide the first characterization of the association between variation in the CP microstructure and macrostructure/volume using advanced magnetic resonance imaging (MRI) methodology, and blood-based biomarkers of Alzheimer's disease (Aß_42/40 ratio; pTau181), neuroinflammation and neuronal injury (GFAP; NfL). We hypothesized that plasma biomarkers of brain pathology are associated with disordered CP structure. Moreover, since cerebral microstructural changes can precede macrostructural changes, we also conjecture that these differences would be evident in the CP microstructural integrity. Our cross-sectional study was conducted on a cohort of 108 well-characterized individuals, spanning 22-94 years of age, after excluding participants with cognitive impairments and non-exploitable MR imaging data. Established automated segmentation methods were used to identify the CP volume/macrostructure using structural MR images, while the microstructural integrity of the CP was assessed using our advanced quantitative high-resolution MR imaging of longitudinal and transverse relaxation times (T₁ and T₂). After adjusting for relevant covariates, positive associations were observed between pTau181, NfL and GFAP and all MRI metrics. These associations reached significance (p<0.05) except for CP volume vs. pTau181 (p=0.14), CP volume vs. NfL (p=0.35), and T₂ vs. NFL (p=0.07). Further, negative associations between Aß_42/40 and all MRI metrics were observed but reached significance only for Aß_42/40 vs. T₂ (p=0.04). These novel findings demonstrate that reduced CP macrostructural and microstructural integrity is positively associated with blood-based biomarkers of AD pathology, neurodegeneration/neuroinflammation and neurodegeneration. Degradation of the CP structure may co-occur with AD pathology and neuroinflammation ahead of clinically detectable cognitive impairment, making the CP a potential structure of interest for early disease detection or treatment monitoring.