title: Association between amylin and amyloid-β peptides in plasma in the context of apolipoprotein E4 allele.
abstract: Amylin, a pancreatic peptide that readily crosses the blood brain barrier (BBB), and amyloid-beta peptide (Aβ), 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 β-sheet secondary structures, binding to the same receptor, and being degraded by the same protease. Thus, amylin may be associated with Aβ, but the nature of their relationship remains unclear. In this study, we used human samples to study the relationship between plasma amylin and Aβ in the context of the apolipoprotein E alleles (ApoE). We found that concentrations of Aβ1-42 (P<0.0001) and Aβ1-40 (P<0.0001) increased with each quartile increase of amylin. Using multivariate regression analysis, the study sample showed that plasma amylin was associated with Aβ1-42 (β = +0.149, SE = 0.025, P<0.0001) and Aβ1-40 (β = +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 Aβ1-42 in plasma was found regardless of the ApoE genotype. In contrast, the relationship between amylin and Aβ1-40 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 Aβ from the brain into blood, thus resulting in increased blood levels of both amylin and Aβ. The positive association between amylin and Aβ, especially Aβ1-42, 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 Aβ, especially Aβ1-40, from the AD brain.
authors: Departments of Psychiatry, Boston University School of Medicine, Boston, Massachusetts, United States of America ; Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, Massachusetts, United States of America ; Alzheimer's Disease Center, Boston University School of Medicine, Boston, Massachusetts, United States of America.
authors: Wei Qiao
authors: WQ
authors: Qiu
authors: Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, Massachusetts, United States of America ; Alzheimer's Disease Center, Boston University School of Medicine, Boston, Massachusetts, United States of America.
authors: Max
authors: M
authors: Wallack
authors: Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, Massachusetts, United States of America.
authors: Michael
authors: M
authors: Dean
authors: McLean Hospital, Harvard Medical School, Belmont, Massachusetts, United States of America.
authors: Elizabeth
authors: E
authors: Liebson
authors: Department of Public Health and Family Medicine, Tufts University, Boston, Massachusetts, United States of America.
authors: Mkaya
authors: M
authors: Mwamburi
authors: Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, Massachusetts, United States of America.
authors: Haihao
authors: H
authors: Zhu
mesh_terms: D000368:Aged; D000483:Alleles; D016229:Amyloid beta-Peptides / Q000097:blood*; D000818:Animals; D053327:Apolipoprotein E4 / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D058228:Islet Amyloid Polypeptide / Q000097:blood*; D008297:Male; D051379:Mice; D015999:Multivariate Analysis; D012044:Regression Analysis
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D015415:Biomarkers; D058228:Islet Amyloid Polypeptide