Journal
JOURNAL OF ALZHEIMERS DISEASE
Volume 26, Issue 4, Pages 755-766Publisher
IOS PRESS
DOI: 10.3233/JAD-2011-110002
Keywords
Alzheimer's disease; catechol O-methyltransferase; COMT; dopamine transporter; excitatory amino acid; frontal cortex; serotonin; vesicular acetylcholine; vesicular glutamate transporter
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Funding
- Harvard Brain Bank, Boston, MA [R24MH068855]
- National Institute on Aging, National Institutes of Health
- NATIONAL INSTITUTE OF MENTAL HEALTH [R24MH068855] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [ZIAAG000428, ZIAAG000148] Funding Source: NIH RePORTER
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Alzheimer's disease (AD) is a neurodegenerative disorder characterized by memory loss and behavioral and psychological symptoms of dementia. An imbalance of different neurotransmitters-glutamate, acetylcholine, dopamine, and serotonin-has been proposed as the neurobiological basis of behavioral symptoms in AD. The molecular changes associated with neurotransmission imbalance in AD are not clear. We hypothesized that altered reuptake of neurotransmitters by vesicular glutamate transporters (VGLUTs), excitatory amino acid transporters (EAATs), the vesicular acetylcholine transporter (VAChT), the serotonin reuptake transporter (SERT), or the dopamine reuptake transporter (DAT) are involved in the neurotransmission imbalance in AD. We tested this hypothesis by examining protein and mRNA levels of these transporters in postmortem prefrontal cortex from 10 AD patients and 10 matched non-AD controls. Compared with controls, protein and mRNA levels of VGLUTs, EAAT1-3, VAChT, and SERT were reduced significantly in AD. Expression of DAT and catechol O-methyltransferase was unchanged. Reduced VGLUTs and EAATs may contribute to an alteration in glutamatergic recycling, and reduced SERT could exacerbate depressive symptoms in AD. The reduced VAChT expression could contribute to the recognized cholinergic deficit in AD. Altered neurotransmitter transporters could contribute to the pathophysiology of AD and are potential targets for therapy.
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