amyloid-beta-peptides and Brain-Infarction

The underlying mechanisms of small vessel disease (SVD) subtypes are diffuse arteriopathy (diffuse-SVD) or microatheroma (focal-SVD). Endothelial dysfunction by beta-amyloid peptide (Abeta) deposition has been associated with lacunar infarcts and leukoaraiosis, but its specific relationship with SVD subtypes is unknown. We hypothesized that plasma Abeta levels can play a different role in SVD subtypes in patients with acute lacunar stroke.. 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 Abeta levels.. Median [quartiles] Abeta(1-40) levels (40.4 [35.1, 50.5] versus 55.1 [42.3, 69.6] pg/mL), but not Abeta(1-42) levels, were significantly higher in the diffuse-SVD group than in focal-SVD group (P<0.001) and control subjects (P<0.001). No differences in Abeta(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 beta-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.. Plasma beta-amyloid(1-40) levels are independently associated with the diffuse-SVD subtype. These results are consistent with the pathophysiological role of fraction Abeta(1-40) in disrupting endothelial vascular function.

Topics: Acute Disease; Aged; Amyloid beta-Peptides; Arterioles; Brain Infarction; Causality; Cerebral Arteries; Cohort Studies; Dementia, Vascular; Endothelial Cells; Female; Humans; Leukoaraiosis; Male; Microcirculation; Middle Aged; Peptide Fragments; Predictive Value of Tests

Microvascular brain injury, typically measured by extent of white matter hyperintensity (WMH) on MRI, is an important contributor to cognitive impairment in the elderly. Recent studies suggest a role for circulating beta-amyloid peptide in microvascular dysfunction and white matter disease.. The authors performed a cross-sectional study of clinical, biochemical, and genetic factors associated with WMH in 54 subjects with Alzheimer disease (AD) or mild cognitive impairment (AD/MCI) and an independent group of 42 subjects with cerebral amyloid angiopathy (CAA). Extent of WMH was determined by computer-assisted volumetric measurement normalized to intracranial size (nWMH). Biochemical measurements included plasma concentrations of the 40- and 42-amino acid species of beta-amyloid (Abeta40 and Abeta42) detected by specific enzyme-linked immunosorbent assays.. Plasma Abeta40 concentrations were associated with nWMH in both groups (correlation coefficient = 0.48 in AD/MCI, 0.42 in CAA, p < or = 0.005). Plasma Abeta40 remained independently associated with nWMH after adjustment for potential confounders among age, hypertension, diabetes, homocysteine, creatinine, folate, vitamin B12, and APOE genotype. The presence of lacunar infarctions was also associated with increased Abeta40 in both groups. nWMH was greater in CAA (19.8 cm3) than AD (11.1 cm3) or MCI (10.0 cm3; p < 0.05 for both comparisons).. Plasma beta-amyloid 40 concentration is independently associated with extent of white matter hyperintensity in subjects with Alzheimer disease, mild cognitive impairment, or cerebral amyloid angiopathy. If confirmed in longitudinal studies, these data would suggest circulating beta-amyloid peptide as a novel biomarker or risk factor for microvascular damage in these common diseases of the elderly.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Amyloid beta-Peptides; Biomarkers; Brain; Brain Infarction; Cerebral Amyloid Angiopathy; Cerebral Arteries; Cerebrovascular Disorders; Cognition Disorders; Cross-Sectional Studies; Female; Humans; Male; Microcirculation; Middle Aged; Nerve Fibers, Myelinated; Peptide Fragments; Predictive Value of Tests; Prognosis