title: Secondary microvascular degeneration in amyloid angiopathy of patients with hereditary cerebral hemorrhage with amyloidosis, Dutch type (HCHWA-D).
abstract: Various secondary microvascular degenerative and inflammatory alterations may complicate cerebral amyloid angiopathy (CAA) and contribute to the morbidity of CAA-associated stroke. We have investigated the severity of CAA-associated microangiopathy in a genetically determined Dutch form of CAA (HCHWA-D) that has major similarities to the type of CAA that more commonly occurs with aging or Alzheimer's disease (AD). The presence and extent of the following vascular abnormalities was assessed: (1) hyalinization/fibrosis, (2) microaneurysm formation, (3) chronic (especially lymphocytic) inflammation, (4) perivascular multinucleated giant cells/granulomatous angiitis, (5) macrophages/histiocytes within the vessel wall, (6) vessel wall calcification, (7) fibrinoid necrosis, 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 of the changes, such as histiocytes in blood vessel walls and the relationship 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' reflective of CAA-associated angiopathy could be obtained. This 'score' was reproducible among several observers. We suggest that it might also be applicable to quantifying severe CAA and related microvascular degenerative changes in patients with AD. beta/A4 immunoreactivity was often sparse and adventitial (or almost absent) in severely hyalinized arterioles and microaneurysms. However, macrophages were prominent in the walls of such vessels and may play a role in the pathogenesis and progression of CAA-related microvasculopathy.
authors.affiliation: Department of Neurology, Leiden University Medical Center, The Netherlands. hvinters@pathology.medsch.ucla.edu
authors.forename: H V
authors.initials: HV
authors.lastname: Vinters
authors.forename: R
authors.initials: R
authors.lastname: Natté
authors.forename: M L
authors.initials: ML
authors.lastname: Maat-Schieman
authors.forename: S G
authors.initials: SG
authors.lastname: van Duinen
authors.forename: I
authors.initials: I
authors.lastname: Hegeman-Kleinn
authors.forename: C
authors.initials: C
authors.lastname: Welling-Graafland
authors.forename: J
authors.initials: J
authors.lastname: Haan
authors.forename: R A
authors.initials: RA
authors.lastname: Roos
mesh_terms: D016229:Amyloid beta-Peptides / Q000032:analysis; D034961:Antigens, Nuclear; D015415:Biomarkers; D001921:Brain / Q000098:blood supply* / Q000473:pathology*; D002196:Capillaries / Q000737:chemistry / Q000473:pathology; D016657:Cerebral Amyloid Angiopathy / Q000473:pathology*; D002536:Cerebral Arteries / Q000737:chemistry / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000473:pathology*; D006801:Humans; D008264:Macrophages / Q000502:physiology; D009687:Nuclear Proteins / Q000032:analysis
chemical_list: D016229:Amyloid beta-Peptides; D034961:Antigens, Nuclear; D015415:Biomarkers; D009687:Nuclear Proteins