Aberrant detergent-insoluble excitatory amino acid transporter 2 accumulates in alzheimer disease

Woltjer, Randall L., Duerson, Kevin, Fullmer, Joseph M., Mookherjee, Paramita, Ryan, Allison M., Montine, Thomas J., Kaye, Jeffrey A., Quinn, Joseph F., Silbert, Lisa, Erten-Lyons, Deniz, Leverenz, James B., Bird, Thomas D., Pow, David V., Tanaka, Kohichi, Watson, G. Stennis and Cook, David G. (2010) Aberrant detergent-insoluble excitatory amino acid transporter 2 accumulates in alzheimer disease. Journal of Neuropathology and Experimental Neurology, 69 7: 667-676. doi:10.1097/NEN.0b013e3181e24adb


Author Woltjer, Randall L.
Duerson, Kevin
Fullmer, Joseph M.
Mookherjee, Paramita
Ryan, Allison M.
Montine, Thomas J.
Kaye, Jeffrey A.
Quinn, Joseph F.
Silbert, Lisa
Erten-Lyons, Deniz
Leverenz, James B.
Bird, Thomas D.
Pow, David V.
Tanaka, Kohichi
Watson, G. Stennis
Cook, David G.
Title Aberrant detergent-insoluble excitatory amino acid transporter 2 accumulates in alzheimer disease
Journal name Journal of Neuropathology and Experimental Neurology   Check publisher's open access policy
ISSN 0022-3069
Publication date 2010-07
Sub-type Article (original research)
DOI 10.1097/NEN.0b013e3181e24adb
Volume 69
Issue 7
Start page 667
End page 676
Total pages 10
Place of publication Baltimore, MD, U.S.A.
Publisher Lippincott Williams & Wilkins
Collection year 2011
Language eng
Abstract Alzheimer disease (AD) is characterized by deposition of amyloid-β, tau, and other specific proteins that accumulate in the brain in detergent-insoluble complexes. Alzheimer disease also involves glutamatergic neurotransmitter system disturbances. Excitatory amino acid transporter 2 (EAAT2) is the dominant glutamate transporter in cerebral cortex and hippocampus. We investigated whether accumulation of detergent-insoluble EAAT2 is related to cognitive impairment and neuropathologic changes in AD by quantifying detergent-insoluble EAAT2 levels in hippocampus and frontal cortex of cognitively normal patients, patients with clinical dementia rating of 0.5 (mildly impaired), and AD patients. Parkinson disease patients served as neurodegenerative disease controls. We found that Triton X-100-insoluble EAAT2 levels were significantly increased in patients withAD compared with controls, whereas Triton X-100-insoluble EAAT2 levels inpatients with clinical dementia rating of 0.5 were intermediately elevatedbetween control and AD subjects. Detergentinsolubility of presenilin-1, a structurally similar protein, did not differ among the groups, thus arguing that EAAT2 detergent insolubility was not causedby nonspecific cellular injury. These findings demonstrate that detergent-insoluble EAAT2 accumulation is a progressive biochemical lesion that correlates with cognitive impairment and neuropathologic changes in AD. These findings lend further support to the idea that dysregulationof the glutamatergic system may play a significant role in AD pathogenesis. © 2010 by the American Association of Neuropathologists, Inc.
Keyword Alzheimer disease
EAAT2
Excitotoxicity
Glutamate
Mild cognitive impairment
Oxidative stress
Protein aggregation
SLC1A2
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2011 Collection
 
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Created: Tue, 22 Feb 2011, 10:09:50 EST by Caroline Irle on behalf of UQ Centre for Clinical Research