Glucose regulates amyloid β production via AMPK

Ting Ting Yang, Yao Shan Shih, Yun-Wen Chen, Yu-Min Kuo, Chu Wan Lee

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Alzheimer’s disease (AD) is the most common form of dementia in the elderly. Accumulation of Aβ peptides in the brain has been suggested as the cause of AD (amyloid cascade hypothesis); however, the mechanism for the abnormal accumulation of Aβ in the brains of AD patients remains unclear. A plethora of evidence has emerged to support a link between metabolic disorders and AD. This study was designed to examine the relationship between energy status and Aβ production. Neuro 2a neuroblastoma cells overexpressing human amyloid precursor protein 695 (APP cells) were cultured in media containing different concentrations of glucose and agonist or antagonist of AMP-activated-protein-kinase (AMPK), a metabolic master sensor. The results showed that concentrations of glucose in the culture media were negatively associated with the activation statuses of AMPK in APP cells, but positively correlated with the levels of secreted Aβ. Modulating AMPK activities affected the production of Aβ. If APP cells were cultured in high glucose medium (i.e., AMPK was inactive), stimulation of AMPK activity decreased the production levels of Aβ. On the contrary, if APP cells were incubated in medium containing no glucose (i.e., AMPK was activated), inhibition of AMPK activity largely increased Aβ production. As AMPK activation is a common defect in metabolic abnormalities, our study supports the premise that metabolic disorders may aggravate AD pathogenesis.

Original languageEnglish
Pages (from-to)1381-1390
Number of pages10
JournalJournal of Neural Transmission
Volume122
Issue number10
DOIs
Publication statusPublished - 2015 Oct 1

Fingerprint

AMP-Activated Protein Kinases
Amyloid
Glucose
Alzheimer Disease
Cultured Cells
Amyloid beta-Protein Precursor
Metabolic Diseases
Brain Diseases
Neuroblastoma
Culture Media
Dementia
Peptides
Brain

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Yang, Ting Ting ; Shih, Yao Shan ; Chen, Yun-Wen ; Kuo, Yu-Min ; Lee, Chu Wan. / Glucose regulates amyloid β production via AMPK. In: Journal of Neural Transmission. 2015 ; Vol. 122, No. 10. pp. 1381-1390.
@article{48cd538dc4204ea89b3ca25d6fd3e617,
title = "Glucose regulates amyloid β production via AMPK",
abstract = "Alzheimer’s disease (AD) is the most common form of dementia in the elderly. Accumulation of Aβ peptides in the brain has been suggested as the cause of AD (amyloid cascade hypothesis); however, the mechanism for the abnormal accumulation of Aβ in the brains of AD patients remains unclear. A plethora of evidence has emerged to support a link between metabolic disorders and AD. This study was designed to examine the relationship between energy status and Aβ production. Neuro 2a neuroblastoma cells overexpressing human amyloid precursor protein 695 (APP cells) were cultured in media containing different concentrations of glucose and agonist or antagonist of AMP-activated-protein-kinase (AMPK), a metabolic master sensor. The results showed that concentrations of glucose in the culture media were negatively associated with the activation statuses of AMPK in APP cells, but positively correlated with the levels of secreted Aβ. Modulating AMPK activities affected the production of Aβ. If APP cells were cultured in high glucose medium (i.e., AMPK was inactive), stimulation of AMPK activity decreased the production levels of Aβ. On the contrary, if APP cells were incubated in medium containing no glucose (i.e., AMPK was activated), inhibition of AMPK activity largely increased Aβ production. As AMPK activation is a common defect in metabolic abnormalities, our study supports the premise that metabolic disorders may aggravate AD pathogenesis.",
author = "Yang, {Ting Ting} and Shih, {Yao Shan} and Yun-Wen Chen and Yu-Min Kuo and Lee, {Chu Wan}",
year = "2015",
month = "10",
day = "1",
doi = "10.1007/s00702-015-1413-5",
language = "English",
volume = "122",
pages = "1381--1390",
journal = "Journal of Neural Transmission",
issn = "0300-9564",
publisher = "Springer Verlag",
number = "10",

}

Glucose regulates amyloid β production via AMPK. / Yang, Ting Ting; Shih, Yao Shan; Chen, Yun-Wen; Kuo, Yu-Min; Lee, Chu Wan.

In: Journal of Neural Transmission, Vol. 122, No. 10, 01.10.2015, p. 1381-1390.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Glucose regulates amyloid β production via AMPK

AU - Yang, Ting Ting

AU - Shih, Yao Shan

AU - Chen, Yun-Wen

AU - Kuo, Yu-Min

AU - Lee, Chu Wan

PY - 2015/10/1

Y1 - 2015/10/1

N2 - Alzheimer’s disease (AD) is the most common form of dementia in the elderly. Accumulation of Aβ peptides in the brain has been suggested as the cause of AD (amyloid cascade hypothesis); however, the mechanism for the abnormal accumulation of Aβ in the brains of AD patients remains unclear. A plethora of evidence has emerged to support a link between metabolic disorders and AD. This study was designed to examine the relationship between energy status and Aβ production. Neuro 2a neuroblastoma cells overexpressing human amyloid precursor protein 695 (APP cells) were cultured in media containing different concentrations of glucose and agonist or antagonist of AMP-activated-protein-kinase (AMPK), a metabolic master sensor. The results showed that concentrations of glucose in the culture media were negatively associated with the activation statuses of AMPK in APP cells, but positively correlated with the levels of secreted Aβ. Modulating AMPK activities affected the production of Aβ. If APP cells were cultured in high glucose medium (i.e., AMPK was inactive), stimulation of AMPK activity decreased the production levels of Aβ. On the contrary, if APP cells were incubated in medium containing no glucose (i.e., AMPK was activated), inhibition of AMPK activity largely increased Aβ production. As AMPK activation is a common defect in metabolic abnormalities, our study supports the premise that metabolic disorders may aggravate AD pathogenesis.

AB - Alzheimer’s disease (AD) is the most common form of dementia in the elderly. Accumulation of Aβ peptides in the brain has been suggested as the cause of AD (amyloid cascade hypothesis); however, the mechanism for the abnormal accumulation of Aβ in the brains of AD patients remains unclear. A plethora of evidence has emerged to support a link between metabolic disorders and AD. This study was designed to examine the relationship between energy status and Aβ production. Neuro 2a neuroblastoma cells overexpressing human amyloid precursor protein 695 (APP cells) were cultured in media containing different concentrations of glucose and agonist or antagonist of AMP-activated-protein-kinase (AMPK), a metabolic master sensor. The results showed that concentrations of glucose in the culture media were negatively associated with the activation statuses of AMPK in APP cells, but positively correlated with the levels of secreted Aβ. Modulating AMPK activities affected the production of Aβ. If APP cells were cultured in high glucose medium (i.e., AMPK was inactive), stimulation of AMPK activity decreased the production levels of Aβ. On the contrary, if APP cells were incubated in medium containing no glucose (i.e., AMPK was activated), inhibition of AMPK activity largely increased Aβ production. As AMPK activation is a common defect in metabolic abnormalities, our study supports the premise that metabolic disorders may aggravate AD pathogenesis.

UR - http://www.scopus.com/inward/record.url?scp=84942985864&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84942985864&partnerID=8YFLogxK

U2 - 10.1007/s00702-015-1413-5

DO - 10.1007/s00702-015-1413-5

M3 - Article

VL - 122

SP - 1381

EP - 1390

JO - Journal of Neural Transmission

JF - Journal of Neural Transmission

SN - 0300-9564

IS - 10

ER -