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Divergent enlarged perivascular spaces volumes in early versus late age-of-onset Alzheimer's disease

Younes, K.; Cobigo, Y.; Tsuie, T.; Wang, E.; Wolf, A.; La Joie, R.; Soleimani-Meigooni, D. N.; Asken, B.; Tosun, D.; Kramer, J. H.; Ferguson, A. R.; Miller, B. L.; Mormino, E. C.; Schwartz, D.; Silbert, L. C.; Rabinovici, G.; Rosen, H.; Elahi, F. M.

2023-08-02 neurology
10.1101/2023.08.01.23293514 medRxiv
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INTRODUCTIONEnlarged perivascular spaces (EPVS) are considered a conduit for the brains waste clearance system. With aging, the brains ability to clear molecules is thought to decline, contributing to the retention of Alzheimers disease (AD) neuropathology. However, the role of EPVS in late-onset AD (LOAD) is complicated by co-morbidities. Early-onset AD (EOAD) offers a unique opportunity to understand the role of EPVS in AD. METHODSAutomatically-segmented EPVS volumes in biomarker-confirmed EOAD (n=58) and LOAD (n=43) and age-matched Controls (n=60) were correlated with amyloid and tau PET and cognition. Linear regression models were used. RESULTSIn LOAD, higher EPVS volumes were associated with better memory and functional performance. However, this association was not observed in EOAD. Additionally, higher tau levels were linked to increased EPVS in LOAD, but not in EOAD. DISCUSSIONEOAD and LOAD demonstrate distinct associations between EPVS, AD hallmarks, and cognition, suggesting differences in EPVSs role in these AD subtypes, necessitating further investigation.

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