Low density of sigma1 receptors in early Alzheimer's disease.
OBJECTIVE
The sigma(1) receptor is considered to be involved in cognitive function. A postmortem study reported that the sigma(1) receptors were reduced in the hippocampus in Alzheimer's disease (AD). However, in vivo imaging of sigma(1) receptors in the brain of AD patients has not been reported. The aim of this study is to investigate the mapping of sigma(1) receptors in AD using [(11)C]SA4503 positron emission tomography (PET).


METHODS
We studied five AD patients and seven elderly volunteers. A dynamic series of decay-corrected PET data acquisition was performed for 90 min starting at the time of the injection of 500 MBq of [(11)C]SA4503. A two-tissue three-compartment model was used to estimate K (1), k (2), k (3), k (4), and the delay between metabolite-corrected plasma and tissue time activity using a Gauss-Newton algorithm. The ratio of k (3) to k (4) was computed as the binding potential (BP), which is linearly related to the density of sigma(1) receptors. Unpaired t tests were used to compare K (1) and BP in patients with AD and normal subjects.


RESULTS
As compared with normals, BP in the AD was significantly lower in the frontal, temporal, and occipital lobe, cerebellum and thalamus, whereas K (1) was significantly lower in the parietal lobe.


CONCLUSIONS
[(11)C]SA4503 PET can demonstrate that the density of cerebral and cerebellar sigma(1) receptors is reduced in early AD.
Mishina
Masahiro
M
Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan. mishina@nms.ac.jp
Ohyama
Masashi
M
Ishii
Kenji
K
Kitamura
Shin
S
Kimura
Yuichi
Y
Oda
Kei-ichi
K
Kawamura
Kazunori
K
Sasaki
Toru
T
Kobayashi
Shiro
S
Katayama
Yasuo
Y
Ishiwata
Kiichi
K
D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000473:pathology*; D001923:Brain Chemistry; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D002531:Cerebellum / Q000000981:diagnostic imaging / Q000473:pathology; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D010879:Piperazines / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D017480:Receptors, sigma / Q000032:analysis* / Q000737:chemistry; D013788:Thalamus / Q000000981:diagnostic imaging / Q000473:pathology; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D010879:Piperazines; D019275:Radiopharmaceuticals; D017480:Receptors, sigma; C101789:SA 4503