Loss of serotonin 2A receptors exceeds loss of serotonergic projections in early Alzheimer's disease: a combined [11C]DASB and [18F]altanserin-PET study.
In patients with Alzheimer's disease (AD), postmortem and imaging studies have revealed early and prominent reductions in cerebral serotonin 2A (5-HT(2A)) receptors. To establish if this was due to a selective disease process of the serotonin system, we investigated the cerebral 5-HT(2A) receptor and the serotonin transporter binding, the latter as a measure of serotonergic projections and neurons. Twelve patients with AD (average Mini Mental State Examination [MMSE]: 24) and 11 healthy age-matched subjects underwent positron emission tomography (PET) scanning with [(18)F]altanserin and [(11)C]N,N-Dimethyl-2-(2-amino-4-cyanopheylthio)benzylamine ([(11)C]DASB). Overall [(18)F]altanserin binding was markedly reduced in AD by 28%-39% (p = 0.02), whereas the reductions in [(11)C]DASB binding were less prominent and mostly insignificant, except for a marked reduction of 33% in mesial temporal cortex (p = .0005). No change in [(11)C]DASB binding was found in the midbrain. We conclude that the prominent reduction in neocortical 5-HT(2A) receptor binding in early AD is not caused by a primary loss of serotonergic neurons or their projections.
Marner
Lisbeth
L
Neurobiology Research Unit, The Neuroscience Centre, Copenhagen, Denmark; Center for Integrated Molecular Brain Imaging, Copenhagen, Denmark. lisbeth.marner@nru.dk
Frokjaer
Vibe G
VG
Kalbitzer
Jan
J
Lehel
Szabolcs
S
Madsen
Karine
K
Baaré
William F C
WF
Knudsen
Gitte M
GM
Hasselbalch
Steen G
SG
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology*; D001596:Benzylamines; D002250:Carbon Radioisotopes; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D007650:Ketanserin / Q000031:analogs & derivatives; D008297:Male; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D049268:Positron-Emission Tomography / Q000379:methods; D011903:Raphe Nuclei / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D044402:Receptor, Serotonin, 5-HT2A / Q000172:deficiency* / Q000378:metabolism; D059326:Serotonergic Neurons / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology*
D001596:Benzylamines; D002250:Carbon Radioisotopes; D005462:Fluorine Radioisotopes; C420885:N,N-dimethyl-2-(2-amino-4-cyanophenylthio)benzylamine; D044402:Receptor, Serotonin, 5-HT2A; C071983:altanserin; D007650:Ketanserin