Increased binding of peripheral benzodiazepine receptor in Alzheimer's disease measured by positron emission tomography with [11C]DAA1106.
BACKGROUND
Peripheral benzodiazepine receptor (PBR) in the brain of Alzheimer's disease (AD) patients has been discussed in relation to the role of gliosis in AD. The PBR was shown to have the ability to reflect activated glial cells, including microglia. The role of activated microglia in AD is an important topic in the pathophysiology of AD. The aim of this study was to quantify PBR in AD brain with a new high-sensitive PBR ligand, [(11)C]DAA1106.


METHODS
Positron emission tomography (PET) scans with [(11)C]DAA1106, a potent and selective ligand for PBR, were performed on 10 patients with AD and 10 age-matched control subjects. All patients had mild to moderate dementia. Duration of illness was 1-3 years at the time of the scans. The PBR binding in the regions of interest was quantified by binding potential (BP) obtained from compartmental model analysis with plasma input function.


RESULTS
Mean BP was increased in the brain of AD patients compared with control subjects in all measured regions. Statistical significance reached across many of the regions examined, including dorsal and medial prefrontal cortex, lateral temporal cortex, parietal cortex, occipital cortex, anterior cingulate cortex, striatum, and cerebellum.


CONCLUSIONS
The broad increase of PBR binding measured with [(11)C]DAA1106 in the brain of AD patients suggests a widespread existence of cellular reactions with PBR in relatively early-stage AD.
Clinical Neuroimaging Section, Department of Molecular Neuroimaging, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan. yasunof@md.tsukuba.ac.jp
Fumihiko
F
Yasuno
Miho
M
Ota
Jun
J
Kosaka
Hiroshi
H
Ito
Makoto
M
Higuchi
Talant K
TK
Doronbekov
Shoko
S
Nozaki
Yota
Y
Fujimura
Michihiko
M
Koeda
Takashi
T
Asada
Tetsuya
T
Suhara
D000081:Acetamides / Q000737:chemistry; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000473:pathology*; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D006801:Humans; D008024:Ligands; D009457:Neuroglia / Q000000981:diagnostic imaging*; D010647:Phenyl Ethers / Q000737:chemistry; D049268:Positron-Emission Tomography / Q000379:methods*; D011485:Protein Binding; D011963:Receptors, GABA-A / Q000378:metabolism*
D000081:Acetamides; C118942:DAA 1106; D008024:Ligands; D010647:Phenyl Ethers; D011963:Receptors, GABA-A