amyloid-beta-peptides and Leukoaraiosis

Alzheimer's disease (AD) commonly accompanies cerebral amyloid angiopathy (CAA).. We aimed to reveal associations between CAA-related brain microbleeds and cerebrospinal fluid (CSF) markers in AD patients.. Patients with probable AD (n = 88) from consecutive patients in our memory clinic were evaluated for patient demographics, vascular risk factors, neuropsychological tests, apolipoprotein E phenotype, MRI including T2*-weighted image and fluid attenuated inversion recovery sequence, and CSF amyloid and tau markers.. The 88 patients with AD included 15 with microbleeds only in cortical/subcortical regions (cortical microbleeds) that could be CAA-related, 16 with microbleeds only in deep locations (deep microbleeds), 3 with microbleeds in both cortical and deep locations (mixed microbleeds), and 54 without microbleeds. The CSF levels of amyloid β-protein 1-40 (Aβ40) and amyloid β-protein 1-42 (Aβ42) were significantly lower in patients with cortical microbleeds than in those without microbleeds (p = 0.001 and p = 0.027, respectively). The result remained unchanged after adjustment for age, sex, apolipoprotein E E4 presence, and leukoaraiosis.. CAA-related cortical microbleeds would be associated with lower CSF levels of Aβ40 and Aβ42 in AD, reflecting the deposition of both Aβ40 and Aβ42 in the cerebrovasculature.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Amyloid beta-Peptides; Apolipoproteins E; Cerebral Amyloid Angiopathy; Female; Humans; Intracranial Hemorrhages; Leukoaraiosis; Magnetic Resonance Imaging; Male; Mental Status Schedule; Middle Aged; Neuropsychological Tests; Peptide Fragments; Retrospective Studies; Risk Factors

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