SECONDARY MICROVASCULAR DEGENERATION IN AMYLOID ANGIOPATHY OF PATIENTS WITH HEREDITARY CEREBRAL-HEMORRHAGE WITH AMYLOIDOSIS, DUTCH TYPE (HCHWA-D)

Various secondary microvascular degenerative and inflammatory alterati ons may complicate cerebral amyloid angiopathy (CAA) and contribute to the morbidity of CAA-associated stroke. We have investigated the seve rity of CAA-associated microangiopathy in a genetically determined Dut ch form of CAA (HCHWA-D) that has major similarities to the type of CA A that more commonly occurs with aging or Alzheimer's disease (AD). Th e presence and extent of the following vascular abnormalities was asse ssed: (1) hyalinization/fibrosis, (2) microaneurysm formation, (3) chr onic (especially lymphocytic) inflammation, (4) perivascular multinucl eated giant cells/granulomatous angiitis, (5) macrophages/histiocytes within the vessel wall, (6) vessel wall calcification, (7) fibrinoid n ecrosis, and (8) mural or occlusive thrombi. (Of these, calcification of CAA-affected vessel walls has, to our knowledge, been described in only a single patient with CAA-associated cerebral hemorrhage.) Some o f the changes, such as histiocytes in blood vessel walls and the relat ionship of vascular hyalinosis to amyloid beta/A4 protein deposition, were highlighted by immunohistochemistry. By assessing the numbers of sections in which the changes were present for each case, a 'score' re flective of CAA-associated angiopathy could be obtained. This 'score' was reproducible among several observers. We suggest that it might als o be applicable to quantifying severe CAA and related microvascular de generative changes in patients with AD. beta/A4 immunoreactivity was o ften sparse and adventitial (or almost absent) in severely hyalinized arterioles and microaneurysms. However, macrophages were prominent in the walls of such vessels and map play a role in the pathogenesis and progression of CAA-related microvasculopathy.