Glial reactions and the clearance of amyloid beta protein in the brains of patients with hereditary cerebral hemorrhage with amyloidosis-Dutch type.
Although the amyloid beta protein (Abeta) E693Q mutation enhances Abeta fibrillization in vitro and cerebral amyloid angiopathy (CAA) in vivo, brain parenchymal Abeta deposition and tau pathology in hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D) are limited. To evaluate whether clearance of Abeta by glial cells may play a role in this regard, this immunohistochemical study of frontal cortex of 14 HCHWA-D autopsy brains was performed using double staining with glial markers and end-specific antibodies to Abetax-42 (Abeta42) and Abetax-40 (Abeta40). Tau pathology was also assessed. Numerous microglia and/or astrocytes carrying cytoplasmic Abeta42(+)40(-) granules were scattered among non-fibrillar (Congo red-negative) Abeta deposits, i.e., clouds, fine diffuse plaques, and Abeta42(+)40(-) dense diffuse plaques. On the other hand, activated microglia and reactive astrocytes associated with fibrillar (Congo red-positive) Abeta deposition, i.e., Abeta42(+)40(+) dense diffuse plaques and CAA invading the parenchyma, were virtually devoid of Abeta granules. Tau pathology was scant and most frequently associated with CAA. These results suggest that relatively non-fibrillar parenchymal Abeta deposits may be liable to glial clearance. Abeta sequestration by glial cells may be a factor limiting the levels of neurotoxic soluble Abeta oligomers in HCHWA-D brain.
Maat-Schieman
Marion L C
ML
Department of Neurology, K5Q 97, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands. M.L.C.Maat-Schieman@lumc.nl
Yamaguchi
Haruyasu
H
Hegeman-Kleinn
Ingrid M
IM
Welling-Graafland
Corrie
C
Natté
Remco
R
Roos
Raymund A C
RA
van Duinen
Sjoerd G
SG
D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D016657:Cerebral Amyloid Angiopathy; D028243:Cerebral Amyloid Angiopathy, Familial / Q000150:complications / Q000378:metabolism / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000150:complications / Q000378:metabolism / Q000473:pathology; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism / Q000473:pathology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D051296:Glucose Transporter Type 5; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009457:Neuroglia / Q000145:classification / Q000473:pathology*; D010446:Peptide Fragments / Q000378:metabolism; D058225:Plaque, Amyloid / Q000378:metabolism; D011180:Postmortem Changes; D016875:tau Proteins / Q000378:metabolism; D000097382:CD68 Molecule
D016229:Amyloid beta-Peptides; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D005904:Glial Fibrillary Acidic Protein; D051296:Glucose Transporter Type 5; D009004:Monosaccharide Transport Proteins; D010446:Peptide Fragments; D016875:tau Proteins; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)