Cerebral small vessel disease-induced apolipoprotein E leakage is associated with Alzheimer disease and the accumulation of amyloid beta-protein in perivascular astrocytes.
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 beta-protein (Abeta) 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, Abeta 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 Abeta in perivascular astrocytes. These results point to an important role of apoE in the perivascular clearance of Abeta 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.
Utter
Sabrina
S
Department of Neuropathology, University of Bonn, Bonn, Germany.
Tamboli
Irfan Y
IY
Walter
Jochen
J
Upadhaya
Ajeet Rijal
AR
Birkenmeier
Gerd
G
Pietrzik
Claus U
CU
Ghebremedhin
Estifanos
E
Thal
Dietmar Rudolf
DR
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001057:Apolipoproteins E / Q000378:metabolism*; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology*; D001808:Blood Vessels / Q000378:metabolism / Q000473:pathology*; D001812:Blood-Brain Barrier / Q000473:pathology; D015153:Blotting, Western; D001921:Brain / Q000098:blood supply / Q000473:pathology; D016657:Cerebral Amyloid Angiopathy / Q000150:complications / Q000473:pathology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007150:Immunohistochemistry; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000378:metabolism; D008297:Male; D008875:Middle Aged
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D007074:Immunoglobulin G; D026503:Low Density Lipoprotein Receptor-Related Protein-1