科研之友
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摘要
Amylin, a pancreatic peptide that readily crosses the blood brain barrier (BBB), and amyloid-beta peptide (A beta), the main component of amyloid plaques and a major component of Alzheimer's disease (AD) pathology in the brain, share several features. These include having similar b-sheet secondary structures, binding to the same receptor, and being degraded by the same protease. Thus, amylin may be associated with Ab, but the nature of their relationship remains unclear. In this study, we used human samples to study the relationship between plasma amylin and Ab in the context of the apolipoprotein E alleles (ApoE). We found that concentrations of A beta 1-42 (p<0.0001) and A beta 1-40 (P<0.0001) increased with each quartile increase of amylin. Using multivariate regression analysis, the study sample showed that plasma amylin was associated with A beta 1-42 (beta= +0.149, SE = 0.025, P<0.0001) and A beta 1-40 (beta = +0.034, SE = 0.016, P = 0.04) as an outcome after adjusting for age, gender, ethnicity, ApoE4, BMI, diabetes, stroke, kidney function and lipid profile. This positive association between amylin and A beta 1-42 in plasma was found regardless of the ApoE genotype. In contrast, the relationship between amylin and A beta 1-40 in plasma seen in ApoE4 non-carriers disappeared in the presence of ApoE4. Using AD mouse models, our recent study demonstrates that intraperitoneal (i. p.) injection of synthetic amylin enhances the removal of A beta from the brain into blood, thus resulting in increased blood levels of both amylin and A beta. The positive association between amylin and Ab, especially A beta 1-42, in human blood samples is probably relevant to the findings in the AD mouse models. The presence of ApoE4 may attenuate amylin's capacity to remove A beta, especially A beta 1-40, from the AD brain.
- 出版日期2014-2-10
