title: Loss of serotonin 5-HT2A receptors in the postmortem temporal cortex correlates with rate of cognitive decline in Alzheimer's disease.
abstract: BACKGROUND
  Previous studies have demonstrated reductions of serotonin 5-HT 2A receptors in the neocortex of Alzheimer's disease (AD) patients. However, it is unclear whether such losses play a role in the cognitive decline of AD.
  
  
  OBJECTIVE
  To correlate neocortical 5-HT 2A receptor alterations with cognitive decline in AD.
  
  
  METHODS
  Postmortem frontal and temporal cortical 5-HT 2A receptors were measured by [3H]ketanserin binding in aged controls as well as in a cohort of AD patients who had been longitudinally assessed for cognitive decline and behavioral symptoms.
  
  
  RESULTS
  5-HT 2A receptor densities in both regions were reduced in severely demented AD patients compared to age-matched controls. In the temporal cortex, this reduction also correlated with the rate of decline of Mini-Mental State Examination (MMSE) scores. The association between 5-HT 2A receptor loss and cognitive decline was independent of the effects of choline acetyltransferase (ChAT) activity and presence of behavioral symptoms.
  
  
  CONCLUSIONS
  Our data suggest that loss of neocortical 5-HT 2A receptors may predict for faster cognitive decline in AD, and point to serotomimetics as potentially useful adjuvants to cholinergic replacement therapies.
authors.affiliation: Dementia Research Laboratory, Department of Clinical Research, Singapore General Hospital, Outram Road, 169608, Singapore.
authors.forename: M K
authors.initials: MK
authors.lastname: Lai
authors.forename: S W
authors.initials: SW
authors.lastname: Tsang
authors.forename: J T
authors.initials: JT
authors.lastname: Alder
authors.forename: J
authors.initials: J
authors.lastname: Keene
authors.forename: T
authors.initials: T
authors.lastname: Hope
authors.forename: M M
authors.initials: MM
authors.lastname: Esiri
authors.forename: P T
authors.initials: PT
authors.lastname: Francis
authors.forename: C P
authors.initials: CP
authors.lastname: Chen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D003072:Cognition Disorders / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D011485:Protein Binding / Q000502:physiology; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D013702:Temporal Lobe / Q000378:metabolism* / Q000473:pathology
chemical_list: D044402:Receptor, Serotonin, 5-HT2A