TY - JOUR
T1 - Brain insulin resistance in type 2 diabetes and Alzheimer disease
T2 - Concepts and conundrums
AU - Arnold, Steven E.
AU - Arvanitakis, Zoe
AU - Macauley-Rambach, Shannon L.
AU - Koenig, Aaron M.
AU - Wang, Hoau Yan
AU - Ahima, Rexford S.
AU - Craft, Suzanne
AU - Gandy, Sam
AU - Buettner, Christoph
AU - Stoeckel, Luke E.
AU - Holtzman, David M.
AU - Nathan, David M.
N1 - Publisher Copyright:
© 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
PY - 2018/3/1
Y1 - 2018/3/1
N2 - 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 alike.
AB - 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 alike.
UR - http://www.scopus.com/inward/record.url?scp=85042632287&partnerID=8YFLogxK
U2 - 10.1038/nrneurol.2017.185
DO - 10.1038/nrneurol.2017.185
M3 - Review article
C2 - 29377010
AN - SCOPUS:85042632287
SN - 1759-4758
VL - 14
SP - 168
EP - 181
JO - Nature Reviews Neurology
JF - Nature Reviews Neurology
IS - 3
ER -