Loss of VGLUT1 and VGLUT2 in the prefrontal cortex is correlated with cognitive decline in Alzheimer disease

Abstract Several lines of evidence suggest that the glutamatergic system is severely impaired in Alzheimer disease (AD). Here, we assessed the status of glutamatergic terminals in AD using the first available specific markers, the vesicular glutamate transporters VGLUT1 and VGLUT2. We quantified VGL...

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Published in:Neurobiology of aging 2008-11, Vol.29 (11), p.1619-1630
Main Authors: Kashani, Alireza, Lepicard, Ève, Poirel, Odile, Videau, Catherine, David, Jean Philippe, Fallet-Bianco, Catherine, Simon, Axelle, Delacourte, André, Giros, Bruno, Epelbaum, Jacques, Betancur, Catalina, El Mestikawy, Salah
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
Alzheimer disease
Alzheimer Disease - complications
Alzheimer Disease - metabolism
Clinical dementia rating scale
Cognition Disorders - complications
Cognition Disorders - metabolism
Female
Human
Humans
Immunoautoradiography
Internal Medicine
Male
Middle Aged
Neurology
Prefrontal cortex
Prefrontal Cortex - metabolism
Statistics as Topic
Vesicular Glutamate Transport Protein 1 - metabolism
Vesicular Glutamate Transport Protein 2 - metabolism
Vesicular glutamate transporters
VGLUT1
VGLUT2
Western blot
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Summary:Abstract Several lines of evidence suggest that the glutamatergic system is severely impaired in Alzheimer disease (AD). Here, we assessed the status of glutamatergic terminals in AD using the first available specific markers, the vesicular glutamate transporters VGLUT1 and VGLUT2. We quantified VGLUT1 and VGLUT2 in the prefrontal dorsolateral cortex (Brodmann area 9) of controls and AD patients using specific antiserums. A dramatic decrease in VGLUT1 and VGLUT2 was observed in AD using Western blot. Similar decreases were observed in an independent group of subjects using immunoautoradiography. The VGLUT1 reduction was highly correlated with the degree of cognitive impairment, assessed with the clinical dementia rating (CDR) score. A significant albeit weaker correlation was also observed with VGLUT2. These findings provide evidence indicating that glutamatergic systems are severely impaired in the A9 region of AD patients and that this impairment is strongly correlated with the progression of cognitive decline. Our results suggest that VGLUT1 expression in the prefrontal cortex could be used as a valuable neurochemical marker of dementia in AD.
ISSN:0197-4580
1558-1497
DOI:10.1016/j.neurobiolaging.2007.04.010