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

The evolvement of amyloid beta (A beta) 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 monoc lonal antibodies to A beta x-42 (A beta 42) or A beta x-40 (A beta 40) and markers for degenerating neurites. A beta 42 immunostaining revealed parenc hymal A beta 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 A beta granules. A beta 40 label ing was absent in clouds/fine diffuse plaques, inconsistent and variably in tense in dense diffuse/coarse plaques and consistent in homogeneous plaques . In a subset of A beta 40-positive plaques, degenerating neurites - withou t tauopathy - and/or amyloid cores were observed. Electron microscopy revea led no apparent amyloid fibrils in fine diffuse plaques, small bundles of f ibrils in dense diffuse/homogeneous plaques, and amyloid masses in coarse p laques. The parenchymal A beta pathology was age-related: the ratio of fine to dense diffuse plaques decreased with age, clouds were limited to younge r patients; coarse plaques to the oldest old. Homogeneous/cored plaques wer e present most consistently in older patients. Plaque density did not incre ase with age. Vascular A beta deposits stained for both A beta species, but exclusively A beta 42-positive, presumably recent deposits were also obser ved. This study suggests that HCHWA-D is a model of plaque evolution in whi ch clouds leave fine diffuse plaques, which may become dense diffuse and ul timately coarse or homogeneous plaques.