Age-related plaque morphology and C-terminal heterogeneity of amyloid β in Dutch-type hereditary cerebral hemorrhage with amyloidosis

• Published in: Acta neuropathologica 2000-04, Vol.99 (4), p.409-419
• Main Authors: MAAT-SCHIEMAN, M. L. C, YAMAGUCHI, H, VAN DUINEN, S. G, NATTE, R, ROOS, R. A. C
• Format: Article
• Language: English
• Subjects: Adult; Age; Aged; Aged, 80 and over; Aging - pathology; Amyloid; Amyloid beta-Peptides - analysis; Amyloidosis; Amyloidosis - pathology; Axons; Biological and medical sciences; Brain - pathology; Brain - ultrastructure; Brain Diseases, Metabolic, Inborn - pathology; Cerebral Amyloid Angiopathy - pathology; Cerebral Arteries - pathology; Cerebral Arteries - ultrastructure; Cerebral cortex; Cerebral Hemorrhage - genetics; Cerebral Hemorrhage - pathology; Clouds; Cortex (frontal); Deposits; Electron microscopy; Female; Fibrils; Hemorrhage; Humans; Male; Medical sciences; Metabolic diseases; Middle Aged; Monoclonal antibodies; Morphology; Neurites - pathology; Neurites - ultrastructure; Neurodegenerative diseases; Neuroglia - pathology; Other metabolic disorders; Plaque, Amyloid - pathology; Plaque, Amyloid - ultrastructure; Plaques; Tau protein
• ISSN: 0001-6322; 1432-0533
• DOI: 10.1007/s004010051143

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.