amyloid-beta-peptides and Stroke

Many stroke patients have pre-existing cognitive impairment. Plasma amyloid β peptides (Aβ) - possible biomarkers of Alzheimer's pathology - induce vascular dysfunction. Our objective was to evaluate factors influencing plasma Aβ1-40 and Aβ1-42 peptides in a cohort of stroke patients. In the Biostroke study (ClinicalTrials.gov Identifier: NCT00763217), we collected vascular risk factors, neuroimaging features and biological tests including Aβ1-40 and Aβ1-42. We used the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) to systematically assess the pre-existing cognitive status. Of 403 patients (371 ischemia), 25 met criteria for pre-existing dementia, 142 for pre-existing cognitive decline-no-dementia, and 236 had no PCoI. Aβ1-42 was independently associated with PCoI (odds ratio 0.973; 95% confidence interval: 0.950-0.996; p=0.024). Factors associated with plasma Aβ1- 40 were age, smoking and diabetes mellitus. After exclusion of hemorrhagic strokes, the results remained unchanged, but blood samples taken less than 12 hours after onset were associated with lower plasma Aβ1-40. Our results support a dissociated response of the 2 plasma Aβ peptides in stroke patients, plasma Aβ1-40 being involved in vascular aspects whereas Aβ1-42 might be involved in neurodegenerative processes.

Topics: Aged; Aged, 80 and over; Amyloid beta-Peptides; Cognition Disorders; Cohort Studies; Female; Humans; Male; Peptide Fragments; Statistics, Nonparametric; Stroke

Amyloid-beta protein (Abeta) plays a key role in Alzheimer disease (AD) and is also implicated in cerebral small vessel disease. Serum total homocysteine (tHcy) is a risk factor for small vessel disease and cognitive impairment and correlates with plasma Abeta levels. To determine whether this association results from a common pathophysiologic mechanism, we investigated whether vitamin supplementation-induced reduction of tHcy influences plasma Abeta levels in the Vitamin Intervention in Stroke Prevention (VISP) study.. Two groups of 150 patients treated with either the high-dose or low-dose formulation of pyridoxine, cobalamin, and folic acid in a randomized, double-blind fashion were selected among the participants in the VISP study without recurrent stroke during follow-up and in the highest 10% of the distribution for baseline tHcy levels. Concentrations of plasma Abeta with 40 (Abeta40) and 42 (Abeta42) amino acids were measured at baseline and at the 2-year visit.. tHcy levels significantly decreased with vitamin supplementation in both groups. tHcy were strongly correlated with Abeta40 but not Abeta42 concentrations. There was no difference in the change in Abeta40, Abeta42 (p = 0.40, p = 0.35), or the Abeta42/Abeta40 ratio over time (p = 0.86) between treatment groups. Abeta measures were not associated with cognitive change.. This double-blind randomized controlled trial of vitamin therapy demonstrates a strong correlation between serum tHcy and plasma Abeta40 concentrations in subjects with ischemic stroke. Treatment with high dose vitamins does not, however, influence plasma levels of Abeta, despite their effect on lowering tHcy. Our results suggest that although tHcy is associated with plasma Abeta40, they may be regulated by independent mechanisms.

Topics: Aged; Amyloid beta-Peptides; Cognition; Dose-Response Relationship, Drug; Double-Blind Method; Down-Regulation; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Osmolar Concentration; Peptide Fragments; Pyridoxine; Stroke; Treatment Failure; Vitamin B 12; Vitamin B Complex; Vitamins

To investigate the changes as well as the related mechanism in cognitive function and levels of serum β-amyloid peptide (Aβ) and brain-derived neurotrophic factor (BDNF) in stroke patients.. A total of 30 patients with acute stroke treated in our hospital from June 2015 to September 2016 were selected as stroke group, while 30 volunteers during the same period were enrolled as control group. Changes in cognitive function of patients were evaluated using the Montreal Cognitive Assessment (MoCA) and mini-mental state examination (MMSE) before and after the treatment. At the same time, the concentrations of serum Aβ1-40 and BDNF were detected, and their correlations with the MMSE score were analyzed. Finally, levels of serum cyclic adenosine monophosphate (cAMP) and phosphorylated-cAMP-response element binding protein (p-CREB), and the phosphorylation level of Tau protein were detected by Western blotting.. MoCA and MMSE scores of patients in stroke group were significantly lower than those in control group (p < 0.01), and the scores were significantly higher in stroke patients after treatment than those before treatment (p < 0.01). Compared with those in control group, the serum Aβ1-40 concentration in patients in stroke group was significantly increased (p < 0.01), but the BDNF level was significantly decreased (p < 0.01). Compared with those before treatment, the serum Aβ1-40 concentration in patients was significantly decreased after treatment (p < 0.01), but the BDNF concentration was significantly increased (p < 0.01). Correlation analysis showed that the MMSE score was negatively correlated with the concentration of Aβ1-40 (r2 = 0.764, p < 0.01), but positively related to the level of BDNF (r2 = 0.827, p < 0.01). Compared with those in control group, the content of serum cAMP and p-CREB in stroke patients was significantly decreased (p < 0.01), but the expression of p-Tau was statistically increased (p < 0.01).. The cognitive function in stroke patients is impaired, with the rising content of serum Aβ1-40 and reduction of BDNF, the mechanism of which is related to the decrease of cAMP and p-CREB and the increase of p-Tau. This provides a theoretical basis for searching the new therapeutic targets and new drugs for stroke.

Topics: Aged; Amyloid beta-Peptides; Biomarkers; Brain-Derived Neurotrophic Factor; Case-Control Studies; Cognition; Cyclic AMP; Cyclic AMP Response Element-Binding Protein; Female; Humans; Male; Middle Aged; Peptide Fragments; Phosphorylation; Prognosis; Stroke; tau Proteins; Time Factors

Recent clinical and experimental studies suggest that ischemic strokes may play an important role in the pathogenesis of Alzheimer's disease (AD). Beta amyloid (Abeta), a major component of senile plaque in AD, is known to be derived from ischemic brain or activated platelets. We prospectively enrolled 62 patients with acute ischemic stroke and 27 age-matched controls. The serum Abeta and P-selectin levels were determined using the Sandwich-ELISA. We divided ischemic strokes into subgroups according to the clinical syndrome, pathogenesis, and infarct size, and compared the Abeta level between each subgroup. The Abeta1-40 level was markedly elevated in ischemic stroke patients, as compared to controls (140.2 +/- 54.0 vs 88.44 +/- 34.96 pg/ml, p<0.001). Cardioembolic and larger artery atherosclerotic infarcts had higher Abeta1-40 level than small vessel disease (p = 0.001). Both infarct size and the initial NIHSS score had significantly positive correlations with the serum level of Abeta1-40 (r = 0.539, p<0.001 and r = 0.425, p = 0.001, respectively). However, the P-selectin level was not significantly correlated with serum Abeta1-40. Our data suggest that elevated circulating Abeta1-40 in ischemic stroke patients may be derived from brain as a consequence of ischemic insults.

Topics: Acute Disease; Aged; Amyloid beta-Peptides; Biomarkers; Brain Ischemia; Female; Humans; Male; Middle Aged; P-Selectin; Peptide Fragments; Platelet Activation; Prospective Studies; Risk Factors; Severity of Illness Index; Stroke