Neuronal insulin signaling and brain structure in nondemented older adults: the Atherosclerosis Risk in Communities Study

NEUROBIOLOGY OF AGING

卷:97

Article

Walker, Keenan A.¹  Chawla, Sahil²  Nogueras-Ortiz, Carlos²  Coresh, Josef³  Sharrett, A. Richey³  Wong, Dean F.⁴  Jack, Clifford R.⁵  Spychalla, Anthony J.⁵  Gottesman, Rebecca F.^1,2  Kapogiannis, Dimitrios^1,2 

[1] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA

[2] NIA, Clin Invest Lab, Intramural Res Program, Baltimore, MD 21224 USA

[3] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA

[4] Washington Univ, Dept Radiol, Mallinckrodt Inst Radiol, Sch Med, St Louis, MS USA

[5] Mayo Clin, Dept Radiol, Rochester, MN USA

关键词: Insulin;    Exosome;    Extracellular vesicle;    Brain;    White matter disease;    Magnetic resonance imaging;   

DOI  :  10.1016/j.neurobiolaging.2020.09.022

来源: Elsevier

【 摘 要 】

We used plasma neuronal extracellular vesicles to examine how neuronal insulin signaling proteins relate cross-sectionally to brain structure in nondemented older adults with varying levels of cortical amyloid. Extracellular vesicles enriched for neuronal origin by anti-L1CAM immunoabsorption were isolated from plasma of Atherosclerosis Risk in Communities-Positron Emission Tomography study participants (n 1/4 88; mean age: 77 years [standard deviation: 6]). Neuronal extracellular vesicle levels of phosphorylated insulin signaling cascade proteins were quantified. Brain volume and white matter hyperintensity (WMH) volume were assessed using 3T magnetic resonance imaging. After adjusting for demographic variables and extracellular vesicle marker Alix, higher levels of a neuronal insulin signaling composite measure were associated with lower WMH and greater temporal lobe volume. Secondary analyses found the levels of downstream protein kinases involved in cell survival (p70S6K) and tau phosphorylation/neuroinflammation (GSK-3 beta) to be most strongly associated with WMH and temporal lobe volume, respectively. Associations between neuronal insulin signaling and lower WMH volume were attenuated in participants with elevated cortical amyloid. These results suggest that enhanced neuronal proximal insulin signaling is associated with preserved brain structure in nondemented older adults. (C) 2020 Elsevier Inc. All rights reserved.

【 授权许可】

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