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

Woltjer, R, Duerson, K, Fullmer, J, Mookherjee, P, Ryan, A, Montine, T, Kaye, J, Quinn, J, Silbert, L, Erten, D, Leverenz, J, Bird, T, Pow, D, tanaka, K, Watson, G and Cook, D 2010, 'Aberrant detergent-insoluble excitatory amino acid transporter 2 accumulates in alzheimer disease', Journal of Neuropathology and Experimental Neurology, vol. 69, no. 7, pp. 667-676.


Document type: Journal Article
Collection: Journal Articles

Title Aberrant detergent-insoluble excitatory amino acid transporter 2 accumulates in alzheimer disease
Author(s) Woltjer, R
Duerson, K
Fullmer, J
Mookherjee, P
Ryan, A
Montine, T
Kaye, J
Quinn, J
Silbert, L
Erten, D
Leverenz, J
Bird, T
Pow, D
tanaka, K
Watson, G
Cook, D
Year 2010
Journal name Journal of Neuropathology and Experimental Neurology
Volume number 69
Issue number 7
Start page 667
End page 676
Total pages 10
Publisher Lippincott Williams & Wilkins
Abstract Alzheimer disease (AD) is characterized by deposition of amyloid-?, 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
Subject Cell Neurochemistry
Keyword(s) Alzheimer disease
EAAT2
Excitotoxicity
Glutamate
Mild cognitive impairment
Oxidative stress
Protein aggregation
SLC1A2
DOI - identifier 10.1097/NEN.0b013e3181e24adb
Copyright notice © 2010 by the American Association of Neuropathologists, Inc.
ISSN 0022-3069
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