TY - JOUR
T1 - Serotonin 1A receptors in the living brain of Alzheimer's disease patients
AU - Kepe, Vladimir
AU - Barrio, Jorge R.
AU - Huang, Sung Cheng
AU - Ercoli, Linda
AU - Siddarth, Prabha
AU - Shoghi-Jadid, Kooresh
AU - Cole, Gregory M.
AU - Satyamurthy, Nagichettiar
AU - Cummings, Jeffrey L.
AU - Small, Gary W.
AU - Phelps, Michael E.
PY - 2006/1/17
Y1 - 2006/1/17
N2 - 4-[F-18]fluoro-N-{2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl} -N-(2-pyridinyl)benzamide, a selective serotonin 1A (5-HT1A) molecular imaging probe, was used in conjunction with positron emission tomography (PET) for quantification of 5-HT1A receptor densities in the living brains of Alzheimer's disease patients (ADs) (n = 8), subjects with mild cognitive impairment (n = 6), and controls (n = 5). ADs had receptor densities significantly decreased in both hippocampi (binding potential: controls 1.62 ± 0.07; ADs 1.18 ± 0.26) and also in raphe nuclei (controls 0.63 ± 0.09; ADs 0.37 ± 0.20). When volume losses are included, 5-HT1A losses are even more severe (i.e., average mean decreases of 24% in mild cognitive impairment patients and 49% in ADs). A strong correlation of 5-HT1A receptor decreases in hippocampus with worsening of clinical symptoms (Mini Mental State Exam scores) was also found. Moreover, these decreases in 5-HT1A receptor measures correlate with decreased glucose utilization as measured with 2-deoxy-2-[F-18]fluoro-D-glucose PET in the brains of ADs (standardized uptake values; globally: controls 0.89 ± 0.04, ADs 0.72 ± 0.04; posterior cingulate gyrus: controls 1.05 ± 0.09, ADs 0.79 ± 0.11). They also inversely correlate with increased neuropathological loads measured with 2-(1-{6-[(2-[F-18]fluoroethyl) (methyl)amino]-2-naphthyl}ethylidene)malononitrile PET in several neocortical regions in the same subjects. The in vivo observations were confirmed independently by in vitro digital autoradiography with 4-[F-18]fluoro-N-{2-[4- (2-methoxyphenyl)-1-piperazinyl]ethyl}-N-(2-pyridinyl)benzamide and 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}-ethylidene) malononitrile on brain tissue specimens from two ADs and three nondemented subjects.
AB - 4-[F-18]fluoro-N-{2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl} -N-(2-pyridinyl)benzamide, a selective serotonin 1A (5-HT1A) molecular imaging probe, was used in conjunction with positron emission tomography (PET) for quantification of 5-HT1A receptor densities in the living brains of Alzheimer's disease patients (ADs) (n = 8), subjects with mild cognitive impairment (n = 6), and controls (n = 5). ADs had receptor densities significantly decreased in both hippocampi (binding potential: controls 1.62 ± 0.07; ADs 1.18 ± 0.26) and also in raphe nuclei (controls 0.63 ± 0.09; ADs 0.37 ± 0.20). When volume losses are included, 5-HT1A losses are even more severe (i.e., average mean decreases of 24% in mild cognitive impairment patients and 49% in ADs). A strong correlation of 5-HT1A receptor decreases in hippocampus with worsening of clinical symptoms (Mini Mental State Exam scores) was also found. Moreover, these decreases in 5-HT1A receptor measures correlate with decreased glucose utilization as measured with 2-deoxy-2-[F-18]fluoro-D-glucose PET in the brains of ADs (standardized uptake values; globally: controls 0.89 ± 0.04, ADs 0.72 ± 0.04; posterior cingulate gyrus: controls 1.05 ± 0.09, ADs 0.79 ± 0.11). They also inversely correlate with increased neuropathological loads measured with 2-(1-{6-[(2-[F-18]fluoroethyl) (methyl)amino]-2-naphthyl}ethylidene)malononitrile PET in several neocortical regions in the same subjects. The in vivo observations were confirmed independently by in vitro digital autoradiography with 4-[F-18]fluoro-N-{2-[4- (2-methoxyphenyl)-1-piperazinyl]ethyl}-N-(2-pyridinyl)benzamide and 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}-ethylidene) malononitrile on brain tissue specimens from two ADs and three nondemented subjects.
KW - Brain 5-HT receptors
KW - Neuronal loss
KW - Positron emission tomography
KW - [F-18]MPPF
UR - http://www.scopus.com/inward/record.url?scp=31444449245&partnerID=8YFLogxK
U2 - 10.1073/pnas.0510237103
DO - 10.1073/pnas.0510237103
M3 - Article
C2 - 16407119
AN - SCOPUS:31444449245
SN - 0027-8424
VL - 103
SP - 702
EP - 707
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 3
ER -