Plasma Amyloid-Beta Levels in a Pre-Symptomatic Dutch-Type Hereditary Cerebral Amyloid Angiopathy Pedigree: A Cross-Sectional and Longitudinal Investigation

Plasma amyloid-beta (Aβ) has long been investigated as a blood biomarker candidate for Cerebral Amyloid Angiopathy (CAA), however previous findings have been inconsistent which could be attributed to the use of less sensitive assays. This study investigates plasma Aβ alterations between pre-symptomatic Dutch-type hereditary CAA (D-CAA) mutation-carriers (MC) and non-carriers (NC) using two Aβ measurement platforms. Seventeen pre-symptomatic members of a D-CAA pedigree were assembled and followed up 3–4 years later (NC = 8; MC = 9). Plasma Aβ1-40 and Aβ1-42 were cross-sectionally and longitudinally analysed at baseline (T1) and follow-up (T2) and were found to be lower in MCs compared to NCs, cross-sectionally after adjusting for covariates, at both T1(Aβ1-40: p = 0.001; Aβ1-42: p = 0.0004) and T2 (Aβ1-40: p = 0.001; Aβ1-42: p = 0.016) employing the Single Molecule Array (Simoa) platform, however no significant differences were observed using the xMAP platform. Further, pairwise longitudinal analyses of plasma Aβ1-40 revealed decreased levels in MCs using data from the Simoa platform (p = 0.041) and pairwise longitudinal analyses of plasma Aβ1-42 revealed decreased levels in MCs using data from the xMAP platform (p = 0.041). Findings from the Simoa platform suggest that plasma Aβ may add value to a panel of biomarkers for the diagnosis of pre-symptomatic CAA, however, further validation studies in larger sample sets are required.

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Evolution of DWI lesions in cerebral amyloid angiopathy

Neurology ◽

10.1212/wnl.0000000000004668 ◽

2017 ◽

Vol 89 (21) ◽

pp. 2136-2142 ◽

Cited By ~ 18

Author(s):

Susanne J. van Veluw ◽

Arne Lauer ◽

Andreas Charidimou ◽

Narimene Bounemia ◽

Li Xiong ◽

...

Keyword(s):

Cerebral Amyloid Angiopathy ◽

Small Vessel Disease ◽

Hemorrhagic Transformation ◽

Superficial Siderosis ◽

Amyloid Angiopathy ◽

Cross Sectional ◽

Small Diffusion ◽

Cerebral Amyloid ◽

Cortical Superficial Siderosis

Objective:To address the pathophysiologic nature of small diffusion-weighted imaging (DWI) lesions in patients with cerebral amyloid angiopathy (CAA) who underwent serial MRI. Specifically, we tested (1) whether DWI lesions occurred preferentially in individuals with prior DWI lesions, (2) the cross-sectional association with chronic cortical cerebral microinfarcts (CMIs), and (3) the evolution of DWI lesions over time.Methods:Patients with probable CAA (n = 79) who underwent at least 2 MRI sessions were included. DWI lesions were assessed at each available time point. Lesion appearance and characteristics were assessed on available structural follow-up images. Presence and burden of other neuroimaging markers of small vessel disease (white matter hyperintensities, cerebral microbleeds, cortical superficial siderosis, and chronic cortical CMIs) were assessed as well.Results:Among 221 DWI scans (79 patients with 2 DWI scans; 40 with ≥3), 60 DWI lesions were found in 28 patients. Patients with DWI lesions at baseline were not more likely to have additional DWI lesions on follow-up compared to patients without DWI lesions at baseline. DWI lesions were associated with chronic cortical CMIs and cortical superficial siderosis, but not with other markers. For 39/60 DWI lesions, >1 MRI sequence was available at follow-up to determine lesion evolution. Twenty-four (62%) were demarcated as chronic lesions on follow-up MRI. Five appeared as cavitations, 18 as noncavitated infarcts, and 1 underwent hemorrhagic transformation.Conclusions:Based on their neuroimaging signature as well as their association with chronic cortical CMIs, DWI lesions appear to have an ischemic origin and represent one part of the CMI spectrum.

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10-Year Follow-Up of a Patient with Cerebral Amyloid Angiopathy

Case Reports in Neurology ◽

10.1159/000501199 ◽

2020 ◽

Vol 12 (Suppl. 1) ◽

pp. 202-206

Author(s):

Min Kyoung Kang ◽

Byung-Woo Yoon

Keyword(s):

Cerebral Amyloid Angiopathy ◽

The Elderly ◽

Amyloid Angiopathy ◽

Spontaneous Intracerebral Hemorrhage ◽

Radiological Features ◽

Magnetic Imaging ◽

Long Term Follow Up ◽

Cerebral Amyloid

We report the case of long-term follow-up of brain magnetic imaging of cerebral amyloid angiopathy. Cerebral amyloid angiopathy is often considered a major cause of spontaneous intracerebral hemorrhage in the elderly. This case illustrates the markedly progressive clinical and radiological features of the vasculopathic process in 10 years.

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3-07-29 Multiple simultaneous hemorrhages caused by slight head trauma in cerebral amyloid angiopathy and its asymptomatic recurrence in the follow-up

Journal of the Neurological Sciences ◽

10.1016/s0022-510x(97)85571-2 ◽

1997 ◽

Vol 150 ◽

pp. S148

Author(s):

R. Rotta Escalante ◽

N. Mendyk ◽

J. Villa ◽

P. Elorza ◽

R. Dominguez ◽

...

Keyword(s):

Head Trauma ◽

Cerebral Amyloid Angiopathy ◽

Amyloid Angiopathy ◽

Cerebral Amyloid

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Abstract P339: Evaluating Ga68 Regional Distribution as a New Pet Tracerfor Diagnosis Cerebral Amyloid Angiopathy

Stroke ◽

10.1161/str.52.suppl_1.p339 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Qihui Zhang ◽

Xiaobin Zhao ◽

Hank F Kung ◽

Zhi Yang ◽

Lin Zhu ◽

...

Keyword(s):

Cerebral Amyloid Angiopathy ◽

Single Molecule ◽

Regional Distribution ◽

Standardized Uptake Value ◽

Initial Assessment ◽

Amyloid Angiopathy ◽

Cerebral Vessel ◽

Total Tau ◽

Pet Ct ◽

Cerebral Amyloid

Introduction: The deposition of β-amyloid in cerebral vessels is an important sign of CAA. Recently, the 68Ga-P14-032 has been used in animal research. It has the ability to selectively bind a β on the cerebral vessel wall, and may become a tracer for CAA. hypothesis: We aimed to investigate the distribution of [ 68 Ga]Ga-P14-032, a novel PET ligand that binds to vascular amyloid, in patients diagnosed clinically with probable cerebral amyloid angiopathy (CAA). Methods: This longitudinal cohort study of 7 subjects (2 probable CAA patients, 2 AD patients, 3 normal subjects) recruited from clinics in China. All participants were aged at least 55 years with underwent [ 68 Ga]Ga-P14-032 PET/CT and PET/MR, a Montreal Cognitive Assessment (Moca) score on initial assessment. The brain PET/CT and PET/MR scans assessed through quantitative analysis. The mean cortical standardized uptake value ratio (SUVr) was calculated using cerebellum as reference. The cortex and white matter were segmented with ITK-Snap based on a T1-weighed image as the mask, leaving the scalp and the blood vessels out of the regions of interest. The corresponding PET volumes were extracted according to the masks obtained on MR and were fused with the MR images, using a MATLAB script. The images were read and interpreted by 2 doctors in nuclear medicine.Plasma levels of total-tau, amyloid-b40 and amyloid-b42 were measured by a single molecule array (Simoa) SR-X analyzer (Quanterix). Results: Positive expression can be seen in the pathological part of microvascular in 2 CAA patients of whom had an ICH. No significant signal was seen in AD subjects or controls. Plasma levels of total-tau, amyloid-b40 and amyloid-b42 were not different among the groups. Conclusions: Our results provide early evidence that the [68Ga]Ga-P14-032 PET probe binds preferentially to vascular amyloid, and may be a useful tracer to diagnostic of CAA. The PET marker was more sensitive to group differences than plasma assays of tau and amyloid.

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Index event of cerebral amyloid angiopathy (CAA) determines long-term prognosis and recurrent events (retrospective analysis and clinical follow-up)

Neurological Research and Practice ◽

10.1186/s42466-021-00152-x ◽

2021 ◽

Vol 3 (1) ◽

Author(s):

Andrea Wagner ◽

Christiane Groetsch ◽

Sibylle Wilfling ◽

Karl-Michael Schebesch ◽

Mustafa Kilic ◽

...

Keyword(s):

Cerebral Amyloid Angiopathy ◽

Recurrent Events ◽

Clinical Presentation ◽

Secondary Prophylaxis ◽

Amyloid Angiopathy ◽

Index Event ◽

Asymptomatic Patients ◽

Cerebral Amyloid

Abstract Background The modified Boston criteria (mBC) define the probability for the diagnosis of cerebral amyloid angiopathy (CAA). Its initial clinical presentation differs from asymptomatic cerebral microbleedings (cMBs), acute ischemic stroke (AIS), cortical hemosiderosis (cSS), to lobar ICH (lICH). Methods Retrospective analyses and clinical follow-ups of individuals with at least mBC “possible” CAA from 2005 to 2018. Results 149 patients were classified in subgroups due to the index event: lICH (n = 91), AIS (n = 32), > 3 cMBs only (n = 16) and cSS (n = 10). Patients in the lICH subgroup had a significantly higher percentage of single new lICHs compared to other groups, whereas patients in the AIS-group had a significantly higher percentage of multiple new AIS. cMBs as index event predisposed for AIS during follow up (p < 0.0016). Patients of the cMBs- or cSS-group showed significantly more TFNEs (transient focal-neurological episodes) and lower numbers of asymptomatic patients (for epilepsy and TFNEs) at the index event than patients with lICH or AIS (p < 0.0013). At long-term follow-up, the cMBs- and cSS-group were characterized by more TFNEs and fewer asymptomatic patients. Conclusions A new classification system of CAA should add subgroups according to the initial clinical presentation to the mBCs allowing individual prognosis, acute treatment and secondary prophylaxis.

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Cortical superficial siderosis and bleeding risk in cerebral amyloid angiopathy

Neurology ◽

10.1212/wnl.0000000000008590 ◽

2019 ◽

Vol 93 (24) ◽

pp. e2192-e2202 ◽

Cited By ~ 5

Author(s):

Andreas Charidimou ◽

Gregoire Boulouis ◽

Steven M. Greenberg ◽

Anand Viswanathan

Keyword(s):

Cerebral Amyloid Angiopathy ◽

Meta Analysis ◽

Bleeding Risk ◽

Superficial Siderosis ◽

Amyloid Angiopathy ◽

Class Iii ◽

Cerebral Amyloid ◽

T2 Mri ◽

Cortical Superficial Siderosis

ObjectiveTo assess the association of cortical superficial siderosis (cSS) presence and extent with future bleeding risk in cerebral amyloid angiopathy (CAA).MethodsThis was a meta-analysis of clinical cohorts of symptomatic patients with CAA who had T2*-MRI at baseline and clinical follow-up for future intracerebral hemorrhage (ICH). We pooled data in a 2-stage meta-analysis using random effects models. Covariate-adjusted hazard ratios (adjHR) from multivariable Cox proportional hazard models were used.ResultsWe included data from 6 eligible studies (n = 1,239). cSS pooled prevalence was 34% (95% confidence interval [CI] 26%–41%; I2 87.94%; p < 0.001): focal cSS prevalence was 14% (95% CI 12%–16%; I2 6.75%; p = 0.37), and disseminated cSS prevalence was 20% (95% CI 13%–26%; I2 90.39%; p < 0.001). During a mean follow-up of 3.1 years (range 1–4 years), 162/1,239 patients experienced a symptomatic ICH-pooled incidence rate 6.9% per year (95% CI 3.9%–9.8% per year; I2 83%; p < 0.001). ICH incidence rates per year according to cSS status were 3.9% (95% CI 1.7%–6.1%; I2 70%; p = 0.018) for patients without cSS, 11.1% (95% CI 7%–15.2%; I2 56.8%; p = 0.074) for cSS presence, 9.1% (95% CI 5.5%–12.8%; I2 0%; p = 0.994) for focal cSS, and 12.5% (95% CI 5.3%–19.7%; I2 73.2%; p = 0.011) for disseminated cSS. In adjusted pooled analysis, any cSS presence was independently associated with increased future ICH risk (adjHR 2.14; 95% CI 1.19–3.85; p < 0.0001). Focal cSS was linked with ICH risk (adjHR 2.11; 95% CI 1.31–2.41; p = 0.002), while disseminated cSS conferred the strongest bleeding risk (adjHR 4.28; 95% CI 2.91–6.30; p < 0.0001).ConclusionIn patients with CAA, cSS presence and extent are the most important MRI prognostic risk factors for future ICH, likely useful in treatment planning.Classification of evidenceThis study provides Class III evidence that in symptomatic CAA survivors with baseline T2*-MRI, cSS (particularly if disseminated, i.e., affecting >3 sulci) increases the risk of future ICH.

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P3-346: CLINICAL SIGNIFICANCE OF AMYLOID BETA POSITIVITY IN PATIENTS WITH CEREBRAL AMYLOID ANGIOPATHY MARKERS

Alzheimer s & Dementia ◽

10.1016/j.jalz.2018.06.1707 ◽

2006 ◽

Vol 14 (7S_Part_23) ◽

pp. P1216-P1217

Author(s):

Hyemin Jang ◽

Young Kyoung Jang ◽

Hee Jin Kim ◽

David J. Werring ◽

Jin San Lee ◽

...

Keyword(s):

Clinical Significance ◽

Cerebral Amyloid Angiopathy ◽

Amyloid Beta ◽

Amyloid Angiopathy ◽

Cerebral Amyloid

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Cortical superficial siderosis multifocality in cerebral amyloid angiopathy

Neurology ◽

10.1212/wnl.0000000000004665 ◽

2017 ◽

Vol 89 (21) ◽

pp. 2128-2135 ◽

Cited By ~ 40

Author(s):

Andreas Charidimou ◽

Gregoire Boulouis ◽

Duangnapa Roongpiboonsopit ◽

Eitan Auriel ◽

Marco Pasi ◽

...

Keyword(s):

Cerebral Amyloid Angiopathy ◽

Interrater Reliability ◽

Superficial Siderosis ◽

Amyloid Angiopathy ◽

Recurrence Rates ◽

Rating Method ◽

Cerebral Amyloid ◽

Annual Risk ◽

Cortical Superficial Siderosis

Objective:In order to explore the mechanisms of cortical superficial siderosis (cSS) multifocality and its clinical implications for recurrent intracerebral hemorrhage (ICH) risk in patients with cerebral amyloid angiopathy (CAA), we used a new rating method that we developed specifically to evaluate cSS extent at spatially separated foci.Methods:Consecutive patients with CAA-related ICH according to Boston criteria from a single-center prospective cohort were analyzed. The new score that assesses cSS multifocality (total range 0–4) showed excellent interrater reliability (k = 0.87). The association of cSS with markers of CAA and acute ICH was investigated. Patients were followed prospectively for recurrent symptomatic ICH.Results:The cohort included 313 patients with CAA. Multifocal cSS prevalence was 21.1%. APOE ε2 allele prevalence was higher in patients with multifocal cSS. In probable/definite CAA, cSS multifocality was independently associated with neuroimaging markers of CAA severity, including lobar microbleeds, but not with acute ICH features, which conversely, were determinants of cSS in possible CAA. During a median follow-up of 2.6 years (interquartile range 0.9–5.1 years), the annual ICH recurrence rates per cSS scores (0–4) were 5%, 6.5%, 13.5%, 16.2%, and 26.9%, respectively. cSS multifocality (presence and spread) was the only independent predictor of increased symptomatic ICH risk (hazard ratio 3.19; 95% confidence interval 1.77–5.75; p < 0.0001).Conclusions:The multifocality of cSS correlates with disease severity in probable CAA; therefore cSS is likely to be caused by discrete hemorrhagic foci. The new cSS scoring system might be valuable for clinicians in determining annual risk of ICH recurrence.

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Early MRI imaging and follow-up study in cerebral amyloid angiopathy

Open Medicine ◽

10.1515/med-2021-0212 ◽

2021 ◽

Vol 16 (1) ◽

pp. 257-263

Author(s):

Shan-chun Zhang ◽

Jian-jun Jia ◽

Heng-li Zhao ◽

Bo Zhou ◽

Wei Wang ◽

...

Keyword(s):

Recurrence Rate ◽

Cerebral Amyloid Angiopathy ◽

Superficial Siderosis ◽

Control Group ◽

Amyloid Angiopathy ◽

Imaging Features ◽

Follow Up Study ◽

Imaging Characteristics ◽

Cerebral Amyloid

Abstract Aim To study the imaging features of leukoaraiosis (LA) and hemorrhage in cerebral amyloid angiopathy (CAA) patients. Methods The earliest MRI images of probable CAA patients and non-CAA patients were collected. The characteristics of LA in the two groups were analyzed. Cerebral micro bleeding (CMB), superficial siderosis (SS), and intracranial hemorrhage (ICH) were recorded in the follow-up study. The space relationship between CMB or SS and ICH was assessed. Results We found that 10/21 (47.6%) patients had occipital prominent LA and 14/21 (66.7%) patients had subcortical punctate LA before the ICH, which was higher than that of the ones in the control group (p = 0.015 and 0.038, respectively). The recurrence rate of ICH was 100% (3/3) in patients with diffuse SS and 36.4% (4/11) in patients without. The recurrence rate of ICH was 60% (3/5) in patients with multiple-lobe CMBs and 44.4% (4/9) in those without. The location of the ICH and CMB was inconsistent. ICH occurred in the ipsilateral cerebral hemisphere of SS in three patients with diffuse SS. Conclusion LA, diffuse SS, and multiple-lobe CMBs are important imaging characteristics of CAA, which may help make early diagnosis and predict the recurrence of ICH.

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