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

[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 (Abeta 42 ) or Abetax-40 (Abeta 40 ) and markers for degenerating neurites . Abeta 42 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 . Abeta 40 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 Abeta 40 -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 Abeta 42 -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 .

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hereditary cerebral hemorrhage with amyloidosis

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