Circulating beta amyloid protein is elevated in patients with acute ischemic stroke

Background and Purpose— It has been proposed that the deposition of the β-amyloid peptide (Aβ) in the brain parenchyma and brain blood vessels has deleterious effects. We tested the hypothesis that the levels of plasma Aβ are related to the outcome in patients with intracerebral hemorrhage. Methods— In a multicenter study, we prospectively included patients with spontaneous intracerebral hemorrhage within the first 24 hours after onset. At admission, we measured plasma Aβ40 and Aβ42 levels using ELISA techniques. Also, we recorded age, sex, vascular risk factors, National Institutes of Health Stroke Scale score, presence of intraventricular hemorrhage, localization, cause, and volume of the hematoma. We obtained the modified Rankin scale and defined a unfavorable outcome as modified Rankin scale >2 at 3 months. Bivariate and multivariate regression analyses were performed. Results— We studied 160 patients (mean age, 73.8±11.3 years; 59.4% of them were men). A favorable outcome was observed in 64 (40%) of the patients. In the bivariate analyses, unfavorable outcome was associated with high age, female sex, diabetes mellitus, presence of intraventricular hemorrhage, high blood glucose, high National Institutes of Health Stroke Scale score, high volume, and high plasma levels of Aβ42 and Aβ40. The multivariate analysis showed that increased age (odds ratio, 1.07; 95% confidence interval, 1.035–1.21; P <0.0001), high admission National Institutes of Health Stroke Scale score (odds ratio, 1.29, 95% confidence interval, 1.17–1.42; P <0.0001), presence of diabetes mellitus (odds ratio, 4.15; 95% confidence interval, 1.21–14.1; P =0.02), and Aβ42 levels >9.7 pg/mL (odds ratio, 4.11; 95% confidence interval, 1.65–10.1; P =0.02) were independently associated with an increased likelihood of an unfavorable outcome. Conclusions— High levels of plasma Aβ42 in patients with acute intracerebral hemorrhage are associated with a poor functional prognosis.

Section: Resultsmentioning

confidence: 99%

Section: Strokementioning

confidence: 99%

Section: Strokementioning

confidence: 99%

See 1 more Smart Citation

Prognostic Value of Plasma β-Amyloid Levels in Patients With Acute Intracerebral Hemorrhage

Martí‐Fàbregas

Delgado‐Mederos

Marín

et al. 2014

“…33 Patients with cardioembolic and large artery atherosclerotic infarcts had higher A␤ 1-40 levels than patients with SVD infarctions, and levels of A␤ 1-40 correlated positively with infarct size and stroke severity. However, this study included only 12 patients classified as SVD and the presence of leukoaraiosis was not analyzed.…”

Section: Gomis Et Al Plasma ␤-Amyloid 1-40 and Small Vessel Disease 3199mentioning

confidence: 87%

Plasma β-Amyloid 1-40 Is Associated With the Diffuse Small Vessel Disease Subtype

Gomis

Sobrino

Ois

et al. 2009

Background and Purpose-The underlying mechanisms of small vessel disease (SVD) subtypes are diffuse arteriopathy (diffuse-SVD) or microatheroma (focal-SVD). Endothelial dysfunction by ␤-amyloid peptide (A␤) deposition has been associated with lacunar infarcts and leukoaraiosis, but its specific relationship with SVD subtypes is unknown. We hypothesized that plasma A␤ levels can play a different role in SVD subtypes in patients with acute lacunar stroke. Methods-We studied 149 patients with acute ischemic stroke of SVD etiology according to Trial Of Org 10172 In Acute Stroke Treatment criteria and 25 age-matched control subjects. Patients were classified into focal-SVD: 39 patients with isolated lacunar infarct without leukoaraiosis and diffuse-SVD: 110 patients with an isolated lacunar infarct with leukoaraiosis or with multiple lacunar infarcts with or without leukoaraiosis. Baseline data included vascular risk factors and extensive laboratory tests, including plasma A␤ levels. Results-Median[quartiles] A␤ 1-40 levels (40.4 [35.1, 50.5] versus 55.1 [42.3, 69.6] pg/mL), but not A␤ 1-42 levels, were significantly higher in the diffuse-SVD group than in focal-SVD group (PϽ0.001) and control subjects (PϽ0.001). No differences in A␤ 1-40 levels were found between focal-SVD and control subjects. Logistic regression analysis showed that age (OR, 1.06; 95% CI, 1.01 to 1.12), history of hypertension (OR, 3.5; 95% CI, 1.3 to 9.2), and plasma ␤-amyloid 1-40 levels over the median value (OR, 17.3; 95% CI, 3.0 to 99 for the third quartile and OR, 6.0; 95% CI, 1.6 to 23 for the fourth quartile) were independently associated with the diffuse-SVD subtype. Key Words: acute stroke Ⅲ beta-amyloid protein Ⅲ leukoaraiosis Ⅲ small vessel disease T he pathogenesis of cerebral small vessel disease (SVD) is incompletely understood. Pathological studies have suggested that there may be 2 types of SVD that can be differentiated on brain imaging. 1 A diffuse arteriopathy of the perforating arteries with hyaline deposition: a pattern referred to as lipohyalinosis (diffuse-SVD) and localized small vessel microatheroma at the origin of the deep perforating arteries (focal-SVD). Diffuse-SVD is associated with multiple small lacunar infarcts with leukoaraiosis and focal-SVD with single large lacunar infarcts without leukoaraiosis. 2,3 Endothelial dysfunction may play an important role in the pathogenesis of the diffuse-SVD subtype. 4 -6 Plasma ␤-amyloid peptide (A␤) is a peptide consisting of either 42 (A␤ 1-42 ) or 40 (A␤ 1-40 ) amino acids derived from a proteolytic processing of the amyloid precursor protein. 7 Insoluble A␤ fibrils are the predominant constituents of senile plaques, one of the pathological hallmarks of Alzheimer disease, 8,9 and of cerebrovascular amyloid in the related condition of cerebral amyloid angiopathy. 10 Plaque amyloid is primarily comprised of A␤ 1-42 , whereas vascular amyloid is formed by the A␤ 1-40 species. Recent evidence suggests that amyloid precursor protein overexpression and A␤ accumulation impair cer...

“…13 In contrast with AD, in which plasma and cerebrospinal fluid A␤ levels are lower, 14,15 serum and cerebrospinal fluid beta amyloid levels have been found to be higher in patients with acute ischemic stroke, suggesting that this increase may be derived from the brain as a consequence of ischemic insult. 16 Higher plasma A␤ was also associated with more lacunar infarcts and white matter lesions in a cross-sectional association study of 1077 participants within the population-based Rotterdam Scan Study 17 and with diffuse small vessel disease subtypes. 18 Plasma A␤ concentration also has been found to be independently associated with white matter hyperintensity in patients with AD, mild cognitive impairment, or cerebral amyloid angiopathy (CAA).…”

Section: Patterns Of Focal Pib Retentionmentioning

confidence: 98%

Subacute Ischemic Stroke Is Associated With Focal ¹¹ C PiB Positron Emission Tomography Retention But Not With Global Neocortical Aβ Deposition

Rowe

Villemagne

et al. 2012

Background and Purpose-Conflicting evidence exists as to whether focal cerebral ischemia contributes to cerebral amyloid deposition. We aimed to look at A␤ deposits, detected by N-methyl-2-(4Ј-methylaminophenyl)-6-hydroxybenzothiazole (PiB) positron emission tomography, in patients with recent ischemic stroke. Specifically, we hypothesized that patients with recent ischemic stroke have higher local and neocortical PiB positron emission tomography retention and that this may be associated with major vascular risk factors. Methods-Ischemic stroke patients were studied using PiB positron emission tomography within 30 days and compared to age-matched controls. Distribution volume ratio maps were created using Logan graphical analysis with the cerebellar cortex as a reference. Results-Among the 21 ischemic stroke patients (median age, 76 years; interquartile range, 68 -77), the ipsilateral peri-infarct region PiB retention was higher compared to the contralateral mirror region, with a PiB distribution volume ratio difference of 0.29 (95% CI, 0.2-0.44; Pϭ0.001) at median 10 (interquartile range, 7-14) days after stroke. Two patients also had higher PiB retention within the infarct compared to the contralateral side. There was no difference in the neocortical PiB retention elsewhere in the brain among ischemic stroke patients compared with 22 age-matched normal controls (Pϭ0.22). Among the risk factors in the ischemic stroke patients, diabetes was associated with a higher neocortical PiB retention (Spearman Rhoϭ0.48; 95% CI, 0.28 -0.72). Conclusions-PiB retention was higher in the peri-infarct region among patients with recent ischemic stroke. This did not translate into a higher global neocortical PiB retention except possibly in patients with diabetes. The cause of the focal PiB retention is uncertain and requires further investigation. (Stroke. 2012;43:1341-1346.)