title: Disturbed neurotransmitter transporter expression in Alzheimer's disease brain.
abstract: 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.
authors: Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
authors: Kevin H
authors: KH
authors: Chen
authors: Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
authors: Edmund A
authors: EA
authors: Reese
authors: Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
authors: Hyung-Wook
authors: HW
authors: Kim
authors: Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
authors: Stanley I
authors: SI
authors: Rapoport
authors: Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
authors: Jagadeesh S
authors: JS
authors: Rao
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D015153:Blotting, Western; D001923:Brain Chemistry / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008566:Membranes / Q000737:chemistry / Q000378:metabolism; D008875:Middle Aged; D050479:Neurotransmitter Transport Proteins / Q000096:biosynthesis* / Q000235:genetics; D058225:Plaque, Amyloid / Q000473:pathology; D017397:Prefrontal Cortex / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D016229:Amyloid beta-Peptides; D050479:Neurotransmitter Transport Proteins; D012333:RNA, Messenger