Serotonin transporters are preserved in the neocortex of anxious Alzheimer's disease patients.
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.
Tsang
Shirley W Y
SW
Neurodegenerative Diseases Program, National Neuroscience Institute, Singapore 169608.
Lai
Mitchell K P
MK
Francis
Paul T
PT
Wong
Peter T-H
PT
Spence
Ian
I
Esiri
Margaret M
MM
Keene
Janet
J
Hope
Tony
T
Chen
Christopher P L-H
CP
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000150:complications / Q000378:metabolism*; D000704:Analysis of Variance; D001007:Anxiety / Q000209:etiology / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D015283:Citalopram / Q000493:pharmacokinetics; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism; D005838:Genotype; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins; D019579:Neocortex / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D011401:Promoter Regions, Genetic / Q000235:genetics; D011869:Radioligand Assay / Q000379:methods; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors / Q000493:pharmacokinetics; D013702:Temporal Lobe / Q000378:metabolism; D014316:Tritium / Q000493:pharmacokinetics
D002352:Carrier Proteins; D015283:Citalopram; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D014316:Tritium; C493230:SLC6A4 protein, human