Brain insulin resistance in type 2 diabetes and Alzheimer disease: concepts and conundrums

被引：1014

作者：

Arnold, Steven E. ^{[1
,2
]}

Arvanitakis, Zoe ^{[3
]}

Macauley-Rambach, Shannon L. ^{[4
]}

Koenig, Aaron M. ^{[1
,2
]}

Wang, Hoau-Yan ^{[5
]}

Ahima, Rexford S. ^{[6
]}

Craft, Suzanne ^{[7
]}

Gandy, Sam ^{[8
,9
,10
]}

Buettner, Christoph ^{[11
]}

Stoeckel, Luke E. ^{[12
,13
,14
]}

Holtzman, David M. ^{[4
]}

Nathan, David M. ^{[12
,13
,14
]}

机构：

[1] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, 114 16th St, Charlestown, MA 02129 USA

[2] Harvard Med Sch, Massachusetts Gen Hosp, Massachusetts Alzheimers Dis Res Ctr, 114 16th St, Charlestown, MA 02129 USA

[3] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, 1750 W Harrison St,Suite 1000, Chicago, IL 60612 USA

[4] Washington Univ, Sch Med, Dept Neurol, Hope Ctr Neurol Disorders, Campus Box 8111,660 S Euclid Ave, St Louis, MO 63110 USA

[5] CUNY, Sch Med, Dept Physiol Pharmacol & Neurosci, 160 Convent Ave, New York, NY 10031 USA

[6] Johns Hopkins Univ, Sch Med, Div Endocrinol Diabet & Metab, 333 East Monument St, Baltimore, MD 21205 USA

[7] Wake Forest Baptist Med Ctr, Wake Forest Sch Med, Gerontol & Geriatr Med Ctr Diabet Obes & Metab, Med Ctr Blvd, Salem, NC 27157 USA

[8] Icahn Sch Med Mt Sinai, Dept Neurol, One Gustave L Levy Pl,Box 1230, New York, NY 10029 USA

[9] Icahn Sch Med Mt Sinai, Dept Psychiat, One Gustave L Levy Pl,Box 1230, New York, NY 10029 USA

[10] Icahn Sch Med Mt Sinai, Mt Sinai Alzheimers Dis Res Ctr, One Gustave L Levy Pl,Box 1230, New York, NY 10029 USA

[11] Icahn Sch Med Mt Sinai, Dept Med, Diabet Obes & Metab Inst, One Gustave L Levy Pl, New York, NY 10029 USA

[12] NIDDK, 6707 Democracy Blvd, Bethesda, MD 20817 USA

[13] Harvard Med Sch, Massachusetts Gen Hosp, Diabet Ctr, Bullfinch 55 Fruit St, Boston, MA 02114 USA

[14] Harvard Med Sch, Massachusetts Gen Hosp, Clin Res Ctr, Bullfinch 55 Fruit St, Boston, MA 02114 USA

来源：

NATURE REVIEWS NEUROLOGY | 2018年 / 14卷 / 03期

关键词：

MILD COGNITIVE IMPAIRMENT; CENTRAL-NERVOUS-SYSTEM; CEREBRAL GLUCOSE-METABOLISM; VASCULAR RISK-FACTORS; GROWTH-FACTOR EXPRESSION; OLDER MEXICAN-AMERICANS; RECEPTOR MESSENGER-RNA; REDUCES FOOD-INTAKE; MIDDLE-AGED ADULTS; PROTEIN-KINASE-B;

D O I：

10.1038/nrneurol.2017.185

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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.

引用

页码：168 / 181

页数：14

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