Title | Targeted Assessment of Enlargement of the Perivascular Space in Alzheimer's Disease and Vascular Dementia Subtypes Implicates Astroglial Involvement Specific to Alzheimer's Disease. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Boespflug, EL, Simon, MJ, Leonard, E, Grafe, M, Woltjer, R, Silbert, LC, Kaye, JA, Iliff, JJ |
Journal | J Alzheimers Dis |
Volume | 66 |
Issue | 4 |
Pagination | 1587-1597 |
Date Published | 2018 |
ISSN | 1875-8908 |
Abstract | Waste clearance from the brain parenchyma occurs along perivascular pathways. Enlargement of the perivascular space (ePVS) is associated with pathologic features of Alzheimer's disease (AD), although the mechanisms and implications of this dilation are unclear. Fluid exchange along the cerebral vasculature is dependent on the perivascular astrocytic water channel aquaporin-4 (AQP4) and loss of perivascular AQP4 localization is found in AD. We directly measured ePVS in postmortem samples of pathologically characterized tissue from participants who were cognitively intact or had AD or mixed dementia (vascular lesions with AD). We found that both AD and mixed dementia groups had significantly increased ePVS compared to cognitively intact subjects. In addition, we found increased global AQP4 expression of the AD group over both control and mixed dementia groups and a qualitative reduction in perivascular localization of AQP4 in the AD group. Among these cases, increasing ePVS burden was associated with the presence of tau and amyloid-β pathology. These findings are consistent with the existing evidence of ePVS in AD and provide novel information regarding differences in AD and vascular dementia and the potential role of astroglial pathology in ePVS. |
DOI | 10.3233/JAD-180367 |
Alternate Journal | J. Alzheimers Dis. |
PubMed ID | 30475760 |
PubMed Central ID | PMC6360949 |
Grant List | K01 AG059842 / AG / NIA NIH HHS / United States P30 AG024978 / AG / NIA NIH HHS / United States P30 AG008017 / AG / NIA NIH HHS / United States R01 AG054456 / AG / NIA NIH HHS / United States P30 NS061800 / NS / NINDS NIH HHS / United States |