Evidence for brain glucose dysregulation in Alzheimer's disease

Yang An; Vijay R. Varma; Sudhir Varma; Ramon Casanova; Eric Dammer; Olga Pletnikova; Chee W. Chia; Josephine M. Egan; Luigi Ferrucci; Juan Troncoso; Allan I. Levey; James Lah; Nicholas T. Seyfried; Cristina Legido-Quigley; Richard O'Brien; Madhav Thambisetty

doi:10.1016/j.jalz.2017.09.011

Evidence for brain glucose dysregulation in Alzheimer's disease

Yang An, Vijay R. Varma, Sudhir Varma, Ramon Casanova, Eric Dammer, Olga Pletnikova, Chee W. Chia, Josephine M. Egan, Luigi Ferrucci, Juan Troncoso, Allan I. Levey, James Lah, Nicholas T. Seyfried, Cristina Legido-Quigley, Richard O'Brien, Madhav Thambisetty

School of Medicine

Research output: Contribution to journal › Article › peer-review

105 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	318-329
Number of pages	12
Journal	Alzheimer's and Dementia
Volume	14
Issue number	3
DOIs	https://doi.org/10.1016/j.jalz.2017.09.011
State	Published - Mar 2018

Keywords

Alzheimer's disease
GLUT1
GLUT3
Glucose
Glycolysis
Insulin resistance
Mass spectrometry
Neuritic plaque
Neurofibrillary tangles

ASJC Scopus subject areas

Clinical Neurology
Geriatrics and Gerontology
Psychiatry and Mental health
Cellular and Molecular Neuroscience
Health Policy
Developmental Neuroscience
Epidemiology

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An, Y., Varma, V. R., Varma, S., Casanova, R., Dammer, E., Pletnikova, O., Chia, C. W., Egan, J. M., Ferrucci, L., Troncoso, J., Levey, A. I., Lah, J., Seyfried, N. T., Legido-Quigley, C., O'Brien, R., & Thambisetty, M. (2018). Evidence for brain glucose dysregulation in Alzheimer's disease. Alzheimer's and Dementia, 14(3), 318-329. https://doi.org/10.1016/j.jalz.2017.09.011

@article{07f4dd54052c4be7be56d116950dc390,

title = "Evidence for brain glucose dysregulation in Alzheimer's disease",

abstract = "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.",

keywords = "Alzheimer's disease, GLUT1, GLUT3, Glucose, Glycolysis, Insulin resistance, Mass spectrometry, Neuritic plaque, Neurofibrillary tangles",

author = "Yang An and Varma, {Vijay R.} and Sudhir Varma and Ramon Casanova and Eric Dammer and Olga Pletnikova and Chia, {Chee W.} and Egan, {Josephine M.} and Luigi Ferrucci and Juan Troncoso and Levey, {Allan I.} and James Lah and Seyfried, {Nicholas T.} and Cristina Legido-Quigley and Richard O'Brien and Madhav Thambisetty",

note = "Funding Information: The authors are grateful to participants in the Baltimore Longitudinal Study of Aging for their invaluable contribution. This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. Support was provided by the Accelerating Medicine Partnership AD grant (grant number: U01AG046161-02 ), the NINDS Emory Neuroscience Core (grant number: P30NS055077 ), and the Emory Alzheimer's Disease Research Center (grant number: P50AG025688 ). The Intramural Research Program of the National Institute on Aging (NIH) had no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. Publisher Copyright: {\textcopyright} 2017 the Alzheimer's Association",

year = "2018",

month = mar,

doi = "10.1016/j.jalz.2017.09.011",

language = "English (US)",

volume = "14",

pages = "318--329",

journal = "Alzheimer's and Dementia",

issn = "1552-5260",

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number = "3",

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TY - JOUR

T1 - Evidence for brain glucose dysregulation in Alzheimer's disease

AU - An, Yang

AU - Varma, Vijay R.

AU - Varma, Sudhir

AU - Casanova, Ramon

AU - Dammer, Eric

AU - Pletnikova, Olga

AU - Chia, Chee W.

AU - Egan, Josephine M.

AU - Ferrucci, Luigi

AU - Troncoso, Juan

AU - Levey, Allan I.

AU - Lah, James

AU - Seyfried, Nicholas T.

AU - Legido-Quigley, Cristina

AU - O'Brien, Richard

AU - Thambisetty, Madhav

N1 - Funding Information: The authors are grateful to participants in the Baltimore Longitudinal Study of Aging for their invaluable contribution. This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. Support was provided by the Accelerating Medicine Partnership AD grant (grant number: U01AG046161-02 ), the NINDS Emory Neuroscience Core (grant number: P30NS055077 ), and the Emory Alzheimer's Disease Research Center (grant number: P50AG025688 ). The Intramural Research Program of the National Institute on Aging (NIH) had no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. Publisher Copyright: © 2017 the Alzheimer's Association

PY - 2018/3

Y1 - 2018/3

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - GLUT1

KW - GLUT3

KW - Glucose

KW - Glycolysis

KW - Insulin resistance

KW - Mass spectrometry

KW - Neuritic plaque

KW - Neurofibrillary tangles

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U2 - 10.1016/j.jalz.2017.09.011

DO - 10.1016/j.jalz.2017.09.011

M3 - Article

C2 - 29055815

AN - SCOPUS:85033232213

SN - 1552-5260

VL - 14

SP - 318

EP - 329

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

IS - 3

ER -

Evidence for brain glucose dysregulation in Alzheimer's disease

Abstract

Keywords

ASJC Scopus subject areas

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