Brain insulin resistance in type 2 diabetes and Alzheimer disease: concepts and conundrums
Steven E. Arnold,Zoe Arvanitakis,Shannon L. Macauley-Rambach,Aaron M. Koenig,Hoau Yan Wang,Rexford S. Ahima,Suzanne Craft,Sam Gandy,Christoph Buettner,Luke E. Stoeckel,David M. Holtzman,David M. Nathan +11 more
TLDR
Key observations and experimental data on insulin signalling in the brain are reviewed and the concept of 'brain insulin resistance' is defined and the growing, although still inconsistent, literature concerning cognitive impairment and neuropathological abnormalities in T2DM, obesity and insulin resistance is reviewed.Abstract:
Considerable overlap has been identified in the risk factors, comorbidities and putative pathophysiological mechanisms of Alzheimer disease and related dementias (ADRDs) and type 2 diabetes mellitus (T2DM), two of the most pressing epidemics of our time Much is known about the biology of each condition, but whether T2DM and ADRDs are parallel phenomena arising from coincidental roots in ageing or synergistic diseases linked by vicious pathophysiological cycles remains unclear Insulin resistance is a core feature of T2DM and is emerging as a potentially important feature of ADRDs Here, we review key observations and experimental data on insulin signalling in the brain, highlighting its actions in neurons and glia In addition, we define the concept of 'brain insulin resistance' and review the growing, although still inconsistent, literature concerning cognitive impairment and neuropathological abnormalities in T2DM, obesity and insulin resistance Lastly, we review evidence of intrinsic brain insulin resistance in ADRDs By expanding our understanding of the overlapping mechanisms of these conditions, we hope to accelerate the rational development of preventive, disease-modifying and symptomatic treatments for cognitive dysfunction in T2DM and ADRDs alikeread more
Citations
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Demonstrated brain insulin resistance in Alzheimer’s disease patients is associated with IGF-1 resistance, IRS-1 dysregulation, and cognitive decline
Konrad Talbot,Hoau-Yan Wang,Hala Kazi,Li-Ying Han,Kalindi Bakshi,Andres Stucky,Robert L. Fuino,Krista R. Kawaguchi,Andrew J. Samoyedny,Robert S. Wilson,Zoe Arvanitakis,Julie A. Schneider,Bryan A. Wolf,David A. Bennett,John Q. Trojanowski,Steven E. Arnold +15 more
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