title: Cerebral serotonin 4 receptors and amyloid-β in early Alzheimer's disease.
abstract: The 5-HT4 receptor may play a role in memory and learning and 5-HT4 receptor activation has been suggested to modulate acetylcholine release and to reduce amyloid-β (Aβ) accumulation. The aim of this study was for the first time to investigate the in vivo cerebral 5-HT4 receptor binding in early Alzheimer disease (AD) patients in relation to cortical Aβ burden. Eleven newly diagnosed untreated AD patients (mean MMSE 24, range 19-27) and twelve age- and gender-matched healthy controls underwent a two-hour dynamic [11C]SB207145 PET scan to measure the binding potential of the 5-HT4 receptor. All AD patients and eight healthy controls additionally underwent a [11C]PIB PET scan to measure the cortical Aβ burden. When AD patients were defined on clinical criteria, no difference in cerebral 5-HT4 receptor binding between AD patients and healthy controls was found (p = 0.54). However, when individuals were reassigned to groups according to their amyloid status, the PIB-positive individuals had 13% higher 5-HT4 receptor levels than PIB-negative individuals (p = 0.02) and the importance of classification of groups is emphasized. The 5-HT4 receptor binding was a positively correlated to Aβ burden (p = 0.03) and negatively to MMSE score of the AD patients (p = 0.02). Our data suggests that cerebral 5-HT4 receptor upregulation starts at a preclinical stage of and continues while dementia is still at a mild stage, which contrasts other receptor subtypes. We speculate that this may either be a compensatory effect of decreased levels of interstitial 5-HT, an attempt to improve cognitive function, increase acetylcholine release or to counteract Aβ accumulation.
authors.affiliation: Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. karine@nru.dk
authors.forename: Karine
authors.initials: K
authors.lastname: Madsen
authors.forename: Wolf-Julian
authors.initials: WJ
authors.lastname: Neumann
authors.forename: Klaus
authors.initials: K
authors.lastname: Holst
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Marner
authors.forename: Mette Thorlund
authors.initials: MT
authors.lastname: Haahr
authors.forename: Szabolcs
authors.initials: S
authors.lastname: Lehel
authors.forename: Gitte Moos
authors.initials: GM
authors.lastname: Knudsen
authors.forename: Steen Gregers
authors.initials: SG
authors.lastname: Hasselbalch
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds; D052160:Benzothiazoles; D001921:Brain / Q000000981:diagnostic imaging; D001923:Brain Chemistry / Q000502:physiology*; D003071:Cognition / Q000502:physiology; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008024:Ligands; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010880:Piperidines; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D044422:Receptors, Serotonin, 5-HT4 / Q000378:metabolism*; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D052160:Benzothiazoles; D008024:Ligands; D010880:Piperidines; D019275:Radiopharmaceuticals; C534709:SB 207145; D013844:Thiazoles; D044422:Receptors, Serotonin, 5-HT4