Abstract
Densities of serotonin transporters (5-HTT) in the postmortem neocortex of behaviorally assessed Alzheimer's disease (AD) patients and aged controls were measured by radioligand binding with [3H]citalopram. It was found that 5-HTT sites in the temporal cortex of AD patients with prominent antemortem anxiety were unaltered compared with controls, but were reduced in non-anxious AD subjects. Furthermore, homozygosity for the high activity allele of a functional polymorphism in the 5-HTT gene promoter region (5-HTTLPR) was associated with both increased [3H]citalopram binding and occurrence of anxiety in the AD subjects. Since serotonin-synthesizing neurons are known to be lost in the AD cortex, this study suggests that the preservation of 5-HTT may exacerbate serotonergic deficits and underlie anxiety symptoms in AD.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Aged
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Aged, 80 and over
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Alleles
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Alzheimer Disease / complications
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Alzheimer Disease / metabolism*
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Analysis of Variance
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Anxiety / etiology
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Anxiety / metabolism*
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Case-Control Studies
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Citalopram / pharmacokinetics
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Female
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Frontal Lobe / metabolism
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Genotype
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Humans
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Male
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / metabolism*
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Membrane Transport Proteins*
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Neocortex / metabolism*
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Nerve Tissue Proteins*
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Promoter Regions, Genetic / genetics
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Radioligand Assay / methods
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Reverse Transcriptase Polymerase Chain Reaction / methods
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Selective Serotonin Reuptake Inhibitors / pharmacokinetics
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Serotonin Plasma Membrane Transport Proteins
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Temporal Lobe / metabolism
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Tritium / pharmacokinetics
Substances
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Carrier Proteins
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Membrane Glycoproteins
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Membrane Transport Proteins
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Nerve Tissue Proteins
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SLC6A4 protein, human
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Serotonin Plasma Membrane Transport Proteins
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Serotonin Uptake Inhibitors
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Citalopram
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Tritium