Cerebral Small Vessel Disease-Induced Apolipoprotein E Leakage Is Associated With Alzheimer Disease and the Accumulation of Amyloid β-Protein in Perivascular Astrocytes

Content Provider	Scilit
Author	Utter, Sabrina Tamboli, Irfan Y. Walter, Jochen Upadhaya, Ajeet Rijal Birkenmeier, Gerd Pietrzik, Claus U. Ghebremedhin, Estifanos Thal, Dietmar Rudolf
Copyright Year	2008
Description	Journal: Journal of Neuropathology and Experimental Neurology Apolipoprotein E (apoE) plays a role in the pathogenesis of Alzheimer disease (AD). It is involved in the receptor-mediated cellular clearance of the amyloid β-protein (Aβ) and in the perivascular drainage of the extracellular fluid. Microvascular changes are also associated with AD and have been discussed as a possible reason for altered perivascular drainage. To further clarify the role of apoE in the perivascular and vascular pathology in AD patients, we studied its occurrence and distribution in the perivascular space, the perivascular neuropil, and in the vessel wall of AD and control cases with and without small vessel disease (SVD). Apolipoprotein E was found in the perivascular space and in the neuropil around arteries of the basal ganglia from control and AD cases disclosing no major differences. Western blot analysis of basal ganglia tissue also revealed no significant differences pertaining to the amount of full-length and C-terminal truncated apoE in AD cases compared with controls. In contrast, Aβ occurred in apoE-positive perivascular astrocytes in AD cases but not in controls. In blood vessels, apoE and immunoglobulin G were detected within the SVD-altered vessel wall. The severity of SVD was associated with the occurrence of apoE in the vessel wall and with that of Aβ in perivascular astrocytes. These results point to an important role of apoE in the perivascular clearance of Aβ in the human brain. The occurrence of apoE and immunoglobulin G in SVD lesions and in the perivascular space suggests that the presence of SVD results in plasma-protein leakage into the brain. It is therefore tempting to speculate that apoE represents a pathogenetic link between SVD and AD.
Related Links	https://academic.oup.com/jnen/article-pdf/67/9/842/9558178/67-9-842.pdf http://jnen.oxfordjournals.org/content/jnen/67/9/842.full.pdf
Ending Page	856
Page Count	15
Starting Page	842
ISSN	00223069
e-ISSN	15546578
DOI	10.1097/nen.0b013e3181836a71
Journal	Journal of Neuropathology and Experimental Neurology
Issue Number	9
Volume Number	67
Language	English
Publisher	Ovid Technologies (Wolters Kluwer Health)
Publisher Date	2008-09-01
Access Restriction	Open
Subject Keyword	Journal: Journal of Neuropathology and Experimental Neurology Small Vessel Vessel Disease Perivascular Astrocytes
Content Type	Text
Resource Type	Article
Subject	Neurology Neurology (clinical) Pathology and Forensic Medicine Cellular and Molecular Neuroscience