title: Plasma amyloid-beta peptide levels correlate with adipocyte amyloid precursor protein gene expression in obese individuals.
abstract: OBJECTIVE
  Several studies have demonstrated that midlife obesity increases the risk for dementia and Alzheimer's disease. Moreover, plasma 42-amino-acid amyloid-beta (Abeta42) levels appear to correlate with BMI. We recently demonstrated that adipocyte amyloid precursor protein (APP) expression is upregulated in obesity and correlates with insulin resistance and adipose tissue inflammation. In this study, we aimed to investigate the relation between adipocyte APP expression and plasma Abeta peptide levels.
  
  
  METHODS
  We conducted a pilot study in which we measured adipocyte APP gene expression and the circulating plasma levels of Abeta40 in 10 obese individuals before and after a 6-month behaviorally based weight loss intervention. Subjects had an oral glucose tolerance test with measurement of insulin levels, Abeta40 levels measured by ELISA and transcript levels of APP in subcutaneous abdominal adipocytes measured by quantitative real-time PCR.
  
  
  RESULTS
  At baseline, adipocyte APP expression correlated significantly with plasma Abeta40 levels and with 2-hour insulin concentrations. Following the 6-month weight loss intervention, body weight and BMI decreased significantly. Fasting plasma concentrations of glucose and insulin were improved. Adipocyte APP expression was significantly decreased (p < 0.001) after weight loss. Changes in adipocyte APP expression correlated with changes in plasma Abeta40 levels (R = 0.74, p = 0.01) and changes in 2-hour insulin (R = 0.75, p = 0.01).
  
  
  CONCLUSIONS
  The results of this pilot study suggest that increased circulating plasma levels of Abeta peptides in obesity may be due to increased adipocyte APP gene expression. While these results suggest a possible mechanism linking midlife obesity with the later development of Alzheimer's disease, further research is necessary to elucidate the regulation and functional significance of APP in adipocytes.
authors: Diabetes and Metabolism Translational Medicine Unit, University of Vermont College of Medicine, Burlington, Vt., USA. ylee325@cu.ac.kr
authors: Yong-Ho
authors: YH
authors: Lee
authors: Julie M
authors: JM
authors: Martin
authors: Rhonda L
authors: RL
authors: Maple
authors: William G
authors: WG
authors: Tharp
authors: Richard E
authors: RE
authors: Pratley
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000097:blood / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D001521:Behavior Therapy; D004797:Enzyme-Linked Immunosorbent Assay; D005215:Fasting / Q000097:blood / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*; D010446:Peptide Fragments / Q000097:blood / Q000378:metabolism*; D010865:Pilot Projects; D016133:Polymerase Chain Reaction; D058255:Protease Nexins; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D007328:Insulin; D010446:Peptide Fragments; D058255:Protease Nexins; D011956:Receptors, Cell Surface; C078592:amyloid beta-protein (1-40)