Age-related plaque morphology and C-terminal heterogeneity of amyloid beta in Dutch-type hereditary cerebral hemorrhage with amyloidosis.
The evolvement of amyloid beta (Abeta) deposition in the frontal cerebral cortex of 24 patients of increasing age with Dutch-type hereditary cerebral hemorrhage with amyloidosis (HCHWA-D) was studied using end-specific monoclonal antibodies to Abetax-42 (Abeta42) or Abetax-40 (Abeta40) and markers for degenerating neurites. Abeta42 immunostaining revealed parenchymal Abeta deposits with a heterogeneous morphology and distribution, i.e., clouds, fine/dense diffuse, coarse, and homogeneous plaques. Clouds and diffuse plaques were associated with glial Abeta granules. Abeta40 labeling was absent in clouds/fine diffuse plaques, inconsistent and variably intense in dense diffuse/coarse plaques and consistent in homogeneous plaques. In a subset of Abeta40-positive plaques, degenerating neurites--without tauopathy--and/or amyloid cores were observed. Electron microscopy revealed no apparent amyloid fibrils in fine diffuse plaques, small bundles of fibrils in dense diffuse/homogeneous plaques, and amyloid masses in coarse plaques. The parenchymal Abeta pathology was age-related: the ratio of fine to dense diffuse plaques decreased with age, clouds were limited to younger patients; coarse plaques to the oldest old. Homogeneous/cored plaques were present most consistently in older patients. Plaque density did not increase with age. Vascular Abeta deposits stained for both Abeta species, but exclusively Abeta42-positive, presumably recent deposits were also observed. This study suggests that HCHWA-D is a model of plaque evolution in which clouds leave fine diffuse plaques, which may become dense diffuse and ultimately coarse or homogeneous plaques.
Maat-Schieman
M L
ML
Department of Neurology, Leiden University Medical Center, The Netherlands. mmaat@neurology.azl.nl
Yamaguchi
H
H
van Duinen
S G
SG
Natté
R
R
Roos
R A
RA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000032:analysis*; D000686:Amyloidosis / Q000473:pathology*; D001921:Brain / Q000473:pathology / Q000648:ultrastructure; D020739:Brain Diseases, Metabolic, Inborn / Q000473:pathology*; D016657:Cerebral Amyloid Angiopathy / Q000473:pathology*; D002536:Cerebral Arteries / Q000473:pathology / Q000648:ultrastructure; D002543:Cerebral Hemorrhage / Q000235:genetics* / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016501:Neurites / Q000473:pathology / Q000648:ultrastructure; D009457:Neuroglia / Q000473:pathology; D058225:Plaque, Amyloid / Q000473:pathology* / Q000648:ultrastructure
D016229:Amyloid beta-Peptides