Search

Background: Hemorrhagic and ischemic magnetic resonance imaging lesions as well as the more recently described decrease in vasomotor reactivity have been suggested as possible biomarkers for cerebral amyloid angiopathy (CAA). Analyses of these markers have been primarily cross-sectional during the symptomatic phase of the disease, with little data on their longitudinal progression, particularly in the presymptomatic phase of the disease when it may be most responsive to treatment. We used the unique opportunity provided by studying Dutch-type hereditary cerebral amyloid angiopathy (D-CAA) to determine longitudinal progression of CAA biomarkers during the presymptomatic as well as the symptomatic phase of the disease. Methods: In this longitudinal case-control study, magnetic resonance imaging markers and cognitive performance were assessed at baseline and after ≈4 years in 10 presymptomatic and 6 symptomatic D-CAA mutation carriers and 20 control subjects. These magnetic resonance imaging markers included hemorrhagic and ischemic manifestations, measurements of cerebral blood flow, and vasomotor reactivity to visual stimulation. Results: In presymptomatic D-CAA mutations carriers, vasomotor reactivity showed a decline over time for blood-oxygen-level–dependent amplitude ( P =0.011) and prolongation of time to peak ( P P =0.007). Conclusions: Our findings indicate that in the presymptomatic phase of D-CAA, cerebrovascular reactivity measured by the blood-oxygen-level–dependent amplitude and time to peak to visual stimulation progressively worsens and can thus be regarded as a disease progression marker. In the symptomatic phase, the most salient marker of progression appears to be recurrent intracerebral hemorrhage.

Background and Purpose- Previous studies of symptomatic and asymptomatic hereditary cerebral amyloid angiopathy (CAA) patients offered the possibility to study the radiological manifestations of CAA in the early stages of the disease. Recently, a striped cortex, observable as hypointense lines perpendicular to the pial surface on T

Background and Purpose— Validation of the Boston criteria for the in vivo diagnosis of cerebral amyloid angiopathy (CAA) is challenging, because noninvasive diagnostic tests do not exist. Hereditary cerebral hemorrhage with amyloidosis–Dutch type is an accepted monogenetic model of CAA and diagnosis can be made with certainty based on DNA analysis. The aim of this study was to analyze and refine the existing Boston criteria in patients with hereditary cerebral hemorrhage with amyloidosis–Dutch type. Methods— We performed T2*-weighted MRI in 27 patients with hereditary cerebral hemorrhage with amyloidosis–Dutch type to assess the presence and location of microbleeds, intracranial hemorrhages, and superficial siderosis. Using the Boston criteria, subjects were categorized as having: no hemorrhages, possible CAA, probable CAA, and hemorrhagic lesions not qualifying for CAA. The sensitivity of the Boston criteria was calculated separately using intracranial hemorrhages only and using intracranial hemorrhages and microbleeds. Results— The sensitivity of the Boston criteria for probable CAA increased from 48% to 63% when microbleeds were included. For symptomatic subjects only, the sensitivity was 100%. No hemorrhages were identified in the deep white matter, basal ganglia, thalamus, or brainstem. Superficial siderosis, observed in 6 patients, did not increase the sensitivity of the Boston criteria in our study group. Conclusions— Our data show that using T2*-weighted MRI and including microbleeds increase the sensitivity of the Boston criteria. The exclusion of hemorrhages in the deep white matter, basal ganglia, thalamus, and brainstem does not lower the sensitivity of the Boston criteria.

Accumulation of amyloid beta-peptide (Abeta) in the central nervous system (CNS) may initiate pathogenic cascades mediating neurovascular and neuronal dysfunctions associated with the development of cerebral beta-amyloidosis and cognitive decline in patients with Alzheimer disease (AD) and with related familial cerebrovascular disorders. Whether Abeta-related pathology in the CNS is reversible or not and what key therapeutic targets are controlling Abeta/amyloid levels in the aging brain remain debatable. In this article, we summarize recent evidence why the receptor for advanced glycation end products and low-density lipoprotein receptor related protein 1 in the vascular CNS barriers are critical for regulation of Abeta homeostasis in the CNS and how altered activities in these 2 receptors at the blood-brain barrier may contribute to the CNS Abeta accumulation resulting in neuroinflammation, disconnect between the cerebral blood flow and metabolism, altered synaptic transmission, neuronal injury, and amyloid deposition into parenchymal and neurovascular lesions. We briefly discuss the potential of advanced glycation end products and low-density lipoprotein receptor related protein 1-based therapeutic strategies to control brain Abeta in animal models of AD and ultimately in patients with AD and related familial cerebrovascular beta-amyloidoses.