scholarly journals Failure of Perivascular Drainage of β-amyloid in Cerebral Amyloid Angiopathy

2014 ◽  
Vol 24 (4) ◽  
pp. 396-403 ◽  
Author(s):  
Cheryl A. Hawkes ◽  
Nimeshi Jayakody ◽  
David A. Johnston ◽  
Ingo Bechmann ◽  
Roxana O. Carare
Keyword(s):  
Cerebral Amyloid Angiopathy ◽  
Amyloid Angiopathy ◽  
Β Amyloid ◽  
Cerebral Amyloid ◽  
Perivascular Drainage

scholarly journals Hereditary cerebral amyloid angiopathy, Piedmont-type mutation

2020 ◽  
Vol 6 (2) ◽  
pp. e411 ◽  
Author(s):  
Mariel G. Kozberg ◽  
Susanne J. van Veluw ◽  
Matthew P. Frosch ◽  
Steven M. Greenberg
Keyword(s):  
Cerebral Amyloid Angiopathy ◽  
Ex Vivo ◽  
Amyloid Plaques ◽  
Amyloid Angiopathy ◽  
Pathologic Examination ◽  
Potential Association ◽  
History Of ◽  
Intracerebral Hemorrhages ◽  
Β Amyloid ◽  
Cerebral Amyloid

ObjectiveWe present here a case report of a patient with a family history of intracerebral hemorrhages (ICHs) who presented with multiple large lobar hemorrhages in rapid succession, with cognitive sparing, who was found to have a mutation in the β-amyloid coding sequence of amyloid precursor protein (Leu705Val), termed the Piedmont-type mutation, the second ever reported case of this form of hereditary cerebral amyloid angiopathy (CAA).MethodsTargeted pathologic examination was performed aided by the use of ex vivo MRI.ResultsSevere CAA was observed mainly involving the leptomeningeal vessels and, to a far lesser extent, cortical vessels, with no amyloid plaques or neurofibrillary tangles.ConclusionsThis leptomeningeal pattern of β-amyloid deposition coupled with multiple large hemorrhages demonstrates unique pathophysiologic characteristics of CAA associated with the Piedmont-type mutation, suggesting a potential association between leptomeningeal CAA and larger ICHs.

scholarly journals Reducing Available Soluble β-Amyloid Prevents Progression of Cerebral Amyloid Angiopathy in Transgenic Mice

2012 ◽  
Vol 71 (11) ◽  
pp. 1009-1017 ◽  
Author(s):  
Julia L. Gregory ◽  
Claudia M. Prada ◽  
Sara J. Fine ◽  
Monica Garcia-Alloza ◽  
Rebecca A. Betensky ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Cerebral Amyloid Angiopathy ◽  
Amyloid Angiopathy ◽  
Β Amyloid ◽  
Cerebral Amyloid

scholarly journals β-Amyloid in CSF

Neurology ◽  
2016 ◽  
Vol 88 (2) ◽  
pp. 169-176 ◽  
Author(s):  
Ellis S. van Etten ◽  
Marcel M. Verbeek ◽  
Jeroen van der Grond ◽  
Ronald Zielman ◽  
Sanneke van Rooden ◽  
...  
Keyword(s):  
Cerebral Amyloid Angiopathy ◽  
Clinical Symptoms ◽  
White Matter Hyperintensity ◽  
Superficial Siderosis ◽  
Csf Biomarkers ◽  
Amyloid Angiopathy ◽  
Cross Sectional ◽  
Mutation Carriers ◽  
Β Amyloid ◽  
Cerebral Amyloid

Objective:To investigate CSF biomarkers in presymptomatic and symptomatic mutation carriers with hereditary cerebral hemorrhage with amyloidosis–Dutch type (HCHWA-D), a model for sporadic cerebral amyloid angiopathy, and to determine the earliest deposited form of β-amyloid (Aβ).Methods:HCHWA-D mutation carriers and controls were enrolled in the cross-sectional EDAN (Early Diagnosis of Amyloid Angiopathy Network) study. The HCHWA-D group was divided into symptomatic carriers with a previous intracerebral hemorrhage and presymptomatic carriers. CSF concentrations of Aβ40, Aβ42, total tau, and phosphorylated tau181 proteins were compared to those of controls of a similar age. Correlations between CSF biomarkers, MRI markers, and age were investigated with multivariate linear regression analyses.Results:We included 10 symptomatic patients with HCHWA-D (mean age 55 ± 6 years), 5 presymptomatic HCHWA-D carriers (mean age 36 ± 13 years), 31 controls <50 years old (mean age 31 ± 7 years), and 50 controls ≥50 years old (mean age 61 ± 8 years). After correction for age, CSF Aβ40 and Aβ42 were significantly decreased in symptomatic carriers vs controls (median Aβ40 1,386 vs 3,867 ng/L, p < 0.001; median Aβ42 289 vs 839 ng/L, p < 0.001) and in presymptomatic carriers vs controls (median Aβ40 3,501 vs 4,684 ng/L, p = 0.011; median Aβ42 581 vs 1,058 ng/L, p < 0.001). Among mutation carriers, decreasing CSF Aβ40 was associated with higher lobar microbleed count (p = 0.010), increasing white matter hyperintensity volume (p = 0.008), and presence of cortical superficial siderosis (p = 0.02).Conclusions:Decreased levels of CSF Aβ40 and Aβ42 occur before HCHWA-D mutation carriers develop clinical symptoms, implicating vascular deposition of both Aβ species as early steps in cerebral amyloid angiopathy pathogenesis. CSF Aβ40 and Aβ42 may serve as preclinical biomarkers of cerebral amyloid angiopathy pathology.

Perivascular drainage of solutes is impaired in the ageing mouse brain and in the presence of cerebral amyloid angiopathy

2011 ◽  
Vol 121 (4) ◽  
pp. 431-443 ◽  
Author(s):  
Cheryl A. Hawkes ◽  
Wolfgang Härtig ◽  
Johannes Kacza ◽  
Reinhard Schliebs ◽  
Roy O. Weller ◽  
...  
Keyword(s):  
Mouse Brain ◽  
Cerebral Amyloid Angiopathy ◽  
Amyloid Angiopathy ◽  
Cerebral Amyloid ◽  
Perivascular Drainage

Florbetapir imaging in cerebral amyloid angiopathy-related hemorrhages

Neurology ◽  
2017 ◽  
Vol 89 (7) ◽  
pp. 697-704 ◽  
Author(s):  
Nicolas Raposo ◽  
Mélanie Planton ◽  
Patrice Péran ◽  
Pierre Payoux ◽  
Fabrice Bonneville ◽  
...  
Keyword(s):  
Cerebral Amyloid Angiopathy ◽  
Brain Mri ◽  
Area Under The Curve ◽  
Standard Uptake Value ◽  
Diagnostic Value ◽  
Amyloid Angiopathy ◽  
Β Amyloid ◽  
Cerebral Amyloid ◽  
Amyloid Tracer ◽  
Pet Amyloid

Objective:To assess whether 18F-florbetapir, a PET amyloid tracer, could bind vascular amyloid in cerebral amyloid angiopathy (CAA) by comparing cortical florbetapir retention during the acute phase between patients with CAA-related lobar intracerebral hemorrhage (ICH) and patients with hypertension-related deep ICH.Methods:Patients with acute CAA-related lobar ICH were prospectively enrolled and compared with patients with deep ICH. 18F-florbetapir PET, brain MRI, and APOE genotype were obtained for all participants. Cortical florbetapir standard uptake value ratio (SUVr) was calculated with the whole cerebellum used as a reference. Patients with CAA and those with deep ICH were compared for mean cortical florbetapir SUVr values.Results:Fifteen patients with acute lobar ICH fulfilling the modified Boston criteria for probable CAA (mean age = 67 ± 12 years) and 18 patients with acute deep ICH (mean age = 63 ± 11 years) were enrolled. Mean global cortical florbetapir SUVr was significantly higher among patients with CAA-related ICH than among patients with deep ICH (1.27 ± 0.12 vs 1.12 ± 0.12, p = 0.001). Cortical florbetapir SUVr differentiated patients with CAA-ICH from those with deep ICH (area under the curve = 0.811; 95% confidence interval [CI] 0.642–0.980) with a sensitivity of 0.733 (95% CI 0.475–0.893) and a specificity of 0.833 (95% CI 0.598–0.948).Conclusions:Cortical florbetapir uptake is increased in patients with CAA-related ICH relative to those with deep ICH. Although 18F-florbetapir PET can label vascular β-amyloid and might serve as an outcome marker in future clinical trials, its diagnostic value in acute CAA-related ICH seems limited in clinical practice.

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