Loss of serotonin 2A receptors exceeds loss of serotonergic projections in early Alzheimer's disease: a combined [(11)C]DASB and [(18)F]altanserin-PET study

TY - JOUR

T1 - Loss of serotonin 2A receptors exceeds loss of serotonergic projections in early Alzheimer's disease: a combined [(11)C]DASB and [(18)F]altanserin-PET study

AU - Marner, Lisbeth

AU - Frokjaer, Vibe G

AU - Kalbitzer, Jan

AU - Lehel, Szabolcs

AU - Madsen, Karine

AU - Baaré, William F C

AU - Knudsen, Gitte M

AU - Hasselbalch, Steen G

N1 - Copyright © 2010 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

JO - Neurobiology of Aging

JF - Neurobiology of Aging

ER -