Evidence for brain glucose dysregulation in Alzheimer's disease

被引：418

作者：

An, Yang ^{[1
]}

Varma, Vijay R. ^{[2
]}

Varma, Sudhir ^{[3
]}

Casanova, Ramon ^{[4
]}

Dammer, Eric ^{[5
]}

Pletnikova, Olga ^{[6
]}

Chia, Chee W. ^{[7
]}

Egan, Josephine M. ^{[8
]}

Ferrucci, Luigi ^{[9
]}

Troncoso, Juan ^{[6
,10
]}

Levey, Allan I. ^{[11
]}

Lah, James ^{[11
]}

Seyfried, Nicholas T. ^{[5
]}

Legido-Quigley, Cristina ^{[12
]}

O'Brien, Richard ^{[13
]}

Thambisetty, Madhav ^{[2
]}

机构：

[1] NIA, Lab Behav Neurosci, NIH, Baltimore, MD 21224 USA

[2] NIA, Clin & Translat Neurosci Unit, Lab Behav Neurosci, NIH, Baltimore, MD 21224 USA

[3] HiThru Analyt, Laurel, MD USA

[4] Wake Forest Univ, Bowman Gray Sch Med, Dept Biostat Sci, Winston Salem, NC USA

[5] Emory Univ, Sch Med, Dept Biochem, Atlanta, GA 30322 USA

[6] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA

[7] NIA, Translat Res & Med Serv Sect, NIH, Baltimore, MD 21224 USA

[8] NIA, Lab Clin Invest, NIH, Baltimore, MD 21224 USA

[9] NIA, Longitudinal Studies Sect, NIH, Baltimore, MD 21224 USA

[10] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA

[11] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA

[12] Kings Coll London, Inst Pharmaceut Sci, London, England

[13] Duke Univ, Sch Med, Dept Neurol, Durham, NC USA

来源：

ALZHEIMERS & DEMENTIA | 2018年 / 14卷 / 03期

关键词：

Glucose; Insulin resistance; Alzheimer's disease; GLUT3; GLUT1; Neuritic plaque; Neurofibrillary tangles; Mass spectrometry; Glycolysis; MILD COGNITIVE IMPAIRMENT; INTRANASAL INSULIN; DIABETES-MELLITUS; IMPROVES COGNITION; ENERGY-METABOLISM; RISK; DEMENTIA; TRANSPORTERS; ADULTS; ABNORMALITIES;

D O I：

10.1016/j.jalz.2017.09.011

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

100204 [神经病学];

摘要：

Introduction: It is unclear whether abnormalities in brain glucose homeostasis are associated with Alzheimer's disease (AD) pathogenesis. Methods: Within the autopsy cohort of the Baltimore Longitudinal Study of Aging, we measured brain glucose concentration and assessed the ratios of the glycolytic amino acids, serine, glycine, and alanine to glucose. We also quantified protein levels of the neuronal (GLUT3) and astrocytic (GLUT1) glucose transporters. Finally, we assessed the relationships between plasma glucose measured before death and brain tissue glucose. Results: Higher brain tissue glucose concentration, reduced glycolytic flux, and lower GLUT3 are related to severity of AD pathology and the expression of AD symptoms. Longitudinal increases in fasting plasma glucose levels are associated with higher brain tissue glucose concentrations. Discussion: Impaired glucose metabolism due to reduced glycolytic flux may be intrinsic to AD pathogenesis. Abnormalities in brain glucose homeostasis may begin several years before the onset of clinical symptoms. (C) 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

引用

页码：318 / 329

页数：12

共 49 条

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