Abstract
Glutamate transporter solute carrier family 1, member 2 (GLT1/EAAT2), a major modulator of glutamate homeostasis in astrocytes, is assessed in post-mortem human brain samples of frontal cortex area 8 in advanced stages of Alzheimer disease (AD) and terminal stages of dementia with Lewy bodies (DLB) in order to gain understanding of astrogliopathy in diseases manifested by dementia. Glial fibrillary acidic protein (GFAP) mRNA expression is significantly increased in AD but not in DLB, whereas GLT1, vesicular glutamate transporter 1 (vGLUT1) and aldehyde dehydrogenase 1 family member 1 (ALDH1L1) are not modified in AD and DLB when compared with controls. GLT1 protein levels are not altered in AD and DLB but GFAP and ALDH1L1 are significantly increased in AD, and GFAP in DLB. As a result, a non-significant decrease in the ratio between GLT1 and GFAP, and between GLT1 and ALDH1L1, is found in both AD and DLB. Double-labeling immunofluorescence and confocal microscopy revealed no visible reduction of GLT1 immunoreactivity in relation to β-amyloid plaques in AD. These data suggest a subtle imbalance between GLT1, and GFAP and ALDH1L1 expression, with limited consequences in glutamate transport.
Highlights
Alzheimer disease (AD), the main cause of dementia in old age, is characterized by β-amyloid deposition forming plaques and amyloid angiopathy, and hyperphosylated tau in neurons with neurofibrillary tangles (NFTs) and pre-tangles, dystrophic neurites of senile plaques, and neuropil threads (Duyckaerts and Dickson, 2011; Ferrer, 2012; Braak and Del Tredici, 2015)
No differences in the expression levels of GLT1 were detected in frontal cortex area 8 in AD and Dementia with Lewy bodies (DLB) when compared with Middle-aged control cases (MA) cases (Figure 1A)
No differences in the expression levels of vesicular glutamate transporter 1 (vGLUT1) were detected in frontal cortex area 8 in AD and DLB when compared with MA (Figure 1B)
Summary
Alzheimer disease (AD), the main cause of dementia in old age, is characterized by β-amyloid deposition forming plaques and amyloid angiopathy, and hyperphosylated tau in neurons with neurofibrillary tangles (NFTs) and pre-tangles, dystrophic neurites of senile plaques, and neuropil threads (Duyckaerts and Dickson, 2011; Ferrer, 2012; Braak and Del Tredici, 2015). Glutamate transporter solute carrier family 1, member 2 (GLT1/EAAT2) expressed in astrocytes regulates glutamate levels at the synapse and plays a cardinal role in preventing excitotoxic neuronal damage in certain neurodegenerative diseases (Nedergaard et al, 2002; Maragakis and Rothstein, 2006). An inverse relation between increased Glial fibrillary acidic protein (GFAP) and reduced GLT1 is described in AD with disease progression as defined by Braak stage of NFT pathology (Simpson et al, 2010, 2011). Altered mRNA and/or protein expression of glutamate transporters have been reported in transgenic models of AD (Masliah et al, 2000; Cassano et al, 2012). Astrocytes in transgenic mice expressing mutant A53T α-synuclein have reduced expression of GLT1 (Gu et al, 2010) but there is no information, as far as we know, regarding GLT1 expression in DLB
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