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

TitleNeuronal insulin signaling and brain structure in nondemented older adults: the Atherosclerosis Risk in Communities Study.
Publication TypeJournal Article
Year of Publication2021
AuthorsWalker KA, Chawla S, Nogueras-Ortiz C, Coresh JJ, Sharrett ARichey, Wong DF, Jack CR, Spychalla AJ, Gottesman RF, Kapogiannis D
JournalNeurobiol Aging
Volume97
Pagination65-72
Date Published2021 Jan
ISSN1558-1497
Abstract

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 = 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-3β) 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.

DOI10.1016/j.neurobiolaging.2020.09.022
Alternate JournalNeurobiol Aging
PubMed ID33160263
PubMed Central IDPMC7736127
Grant ListU01 HL096917 / HL / NHLBI NIH HHS / United States
U01 HL096902 / HL / NHLBI NIH HHS / United States
HHSN268201700002C / HL / NHLBI NIH HHS / United States
HHSN268201700001I / HL / NHLBI NIH HHS / United States
HHSN268201700004I / HL / NHLBI NIH HHS / United States
U01 HL096814 / HL / NHLBI NIH HHS / United States
R01 HL070825 / HL / NHLBI NIH HHS / United States
HHSN268201700003I / HL / NHLBI NIH HHS / United States
U01 HL096812 / HL / NHLBI NIH HHS / United States
K23 AG064122 / AG / NIA NIH HHS / United States
HHSN268201700005C / HL / NHLBI NIH HHS / United States
HHSN268201700001C / HL / NHLBI NIH HHS / United States
HHSN268201700003C / HL / NHLBI NIH HHS / United States
U01 HL096899 / HL / NHLBI NIH HHS / United States
HHSN268201700004C / HL / NHLBI NIH HHS / United States
K24 AG052573 / AG / NIA NIH HHS / United States
HHSN268201700002I / HL / NHLBI NIH HHS / United States
HHSN268201700005I / HL / NHLBI NIH HHS / United States