TY - JOUR
T1 - Loss of serotonin 2A receptors exceeds loss of serotonergic projections in early Alzheimer's disease
T2 - a combined [11C]DASB and [18F]altanserin-PET study
AU - Marner, Lisbeth
AU - Frøkjær, Vibe
AU - Kalbitzer, Jan
AU - Lehel, Szabolcs
AU - Madsen, Karine
AU - Baaré, William F C
AU - Knudsen, Gitte M
AU - Hasselbalch, Steen G
N1 - Copyright © 2012 Elsevier Inc. All rights reserved.
PY - 2012/3
Y1 - 2012/3
N2 - 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.
AB - 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.
U2 - 10.1016/j.neurobiolaging.2010.03.023
DO - 10.1016/j.neurobiolaging.2010.03.023
M3 - Journal article
C2 - 20510480
SN - 0197-4580
VL - 33
SP - 479
EP - 487
JO - Neurobiology of Aging
JF - Neurobiology of Aging
IS - 3
ER -