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PERIVASCULAR SPACE MORPHOLOGY PREDICTS GLIAL TAU ACCUMULATION AND NEGATIVELY CORRELATES WITH NEUROFILAMENT LIGHT LEVEL

Session Type
SYMPOSIUM
Date
Fri, 18.03.2022
Session Time
05:15 PM - 07:15 PM
Room
ONSITE: 133-134
Lecture Time
06:00 PM - 06:15 PM

Abstract

Aims

Perivascular space (PVS) alteration, as captured by MRI, is one of the pathological findings in Alzheimer’s disease (AD). Validation of PVS against neuropathology and histopathology is missing. Therefore, the utility of the PVS imaging as a specific marker of AD pathology has been hindered. Here, we investigate the association of PVS morphology with neurofilament light (NfL) level in CSF and various AD-related postmortem histopathological findings.

Methods

ADNI data was used for this validation study. Two sub-groups were analyzed: 1) participants with MRI and CSF NfL data, 2) participants with premortem MRI and postmortem histology (including Amyloid-B, Tau, neuronal loss, and CAA). White matter and Basal ganglia (BG) PVS were automatically mapped. We used linear regression to assess if PVS morphology is a predictor of CSF-NfL or postmortem AD pathology, correcting of age, sex, and postmortem interval.

Results

PVS morphology was a predictor of CSF-NfL (t=-2.008, p=0.048). BG PVS morphology was a predictor of glial Tau pathology in the superior and middle temporal gyri (t=4.1, p=0.00003) and the parahippocampal gyrus (t=3.5, p=0.0005) and Entorhinal Cortex (t=3.14, p=0.002). PVS volume fraction in white matter was a predictor of vascular pathology, including CAA in the Amygdala (t=2.6, p=0.008) and Entorhinal cortex (t=2.9, p=0.003).

Conclusions

We found that PVS morphology is a predictor of glial Tau aggregation, but not neuronal Tau aggregation, suggesting that PVS alteration is an indicative of the disruption of brain homeostasis. We also observed that individuals with higher PVS volume fraction in BG have lower NfL load, an observation that demands further investigation.

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