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

INTRODUCTION Enlarged perivascular spaces (EPVS) are considered a conduit for the brain’s waste clearance system. With aging, the brain’s ability to clear molecules is thought to decline, contributing to the retention of Alzheimer’s 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. METHODS Automatically-segmented EPVS volumes in biomarker-confirmed EOAD ( n =58), LOAD ( n =43), and age-matched controls ( n =60) were correlated with amyloid and tau PET and cognition. Linear regression models were used. RESULTS In LOAD, higher EPVS volumes were associated with better memory and functional performance. However, this association was not observed in EOAD. Additionally, higher tau was linked to increased EPVS in LOAD, but not in EOAD. DISCUSSION EOAD and LOAD demonstrate distinct associations between EPVS, AD hallmarks, and cognition, suggesting differences in EPVS’s role in these AD subtypes, necessitating further investigation. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by P30AG062422, P30AG066518. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee/IRB of University of California, San Francisco gave ethical approval for this work I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data for this study are available on request * AD : Alzheimer’s Disease BPF : Brain Parenchymal Fraction EPVS : Enlarged perivascular spaces EOAD : Early Onset Alzheimer’s Disease FTP : flortaucipir LOAD : Late Onset Alzheimer’s Disease PiB : Pittsburgh Compound-B.