Increased Binding of Peripheral Benzodiazepine Receptor in Alzheimer's Disease Measured by Positron Emission Tomography with [C-11]DAA1106

Clinical Neuroimaging Section, Department of Molecular Neuroimaging, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
Biological psychiatry (Impact Factor: 10.26). 06/2008; 64(10):835-41. DOI: 10.1016/j.biopsych.2008.04.021
Source: PubMed


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.
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.
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.
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.

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Available from: Fumihiko Yasuno, Jul 23, 2014
    • "Furthermore, stratification for genotype is still required. In an earlier study using [ 11 C]DAA1106, tracer binding was shown to be increased in AD patients [44]. The affinity of its fluorine-18 labelled analogue [ 18 F]FEDAA1106 for TSPO is two-fold higher, but Varrone et al. did not find evidence of increased uptake in AD patients [45] . "
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    • "For example, this method was used recently to demonstrate widespread neuroinflammation in patients with mild cognitive impairment and Alzheimer's Disease (AD) compared to agematched controls [11]. Similarly, a prior study found increased [ 11 C] DAA1106 binding in participants with AD compared with control subjects across many regions, including dorsal and medial prefrontal cortex, lateral temporal cortex, parietal cortex, occipital cortex, anterior cingulate cortex, striatum, and cerebellum [12]. [(3)H] DAA1106 binding was also found to be elevated in a rat model of traumatic brain injury [13] [14]. "
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    • "Among second generation TSPO radioligands, increased binding of [11C]DAA1106 has been observed in AD, as compared to controls, though no correlation was found with respect to disease severity [75]. In a follow-up study among patients with MCI, the increased binding was associated with progression to AD over a 5-year follow-up period [39]. "
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