Elsevier

Biological Psychiatry

Volume 64, Issue 10, 15 November 2008, Pages 835-841
Biological Psychiatry

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

https://doi.org/10.1016/j.biopsych.2008.04.021Get rights and content

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, [11C]DAA1106.

Methods

Positron emission tomography (PET) scans with [11C]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 [11C]DAA1106 in the brain of AD patients suggests a widespread existence of cellular reactions with PBR in relatively early-stage AD.

Section snippets

Participants

The patients were recruited from the outpatient units of university-affiliated psychiatric hospitals and the psychiatric divisions of general hospitals. The healthy subjects were recruited among those participating in a community-based prospective cohort study performed in Ibaragi prefecture in Japan. Demographic and clinical data of the participants are presented in Table 1. We studied 10 healthy control subjects (3 women, 7 men) between 55 and 73 years old (67.9 ± 5.0 years; mean ± SD) and 10

Results

Mean %SUV images of a control subject and an AD patient are shown in Figure 2. Higher uptake of [11C]DAA1106 in the brain was observed in the AD patient compared with the aged normal subject.

The mean values of K1k4 parameters across measured regions in control subjects and patients were .053 ± .005 and .049 ± .005 for K1, .073 ± .003 and .080 ± .005 for k2, .048 ± .002 and .053 ± .004 for k3, and .011± .001 and .010 ± .001 for k4, respectively. For K1k4 values, ANOVA of each value for control

Discussion

In this study, [11C]DAA1106 binding to PBR was significantly increased in various regions in patients with AD at a relatively early stage. Providing that the affinity of radiotracer to PBR did not differ between the groups, our finding might be attributable to the higher number of PBR in these brain regions, which might reflect mainly the activated glial cells that were observed in the brain pathology of AD (8, 9).

Several confounding factors need to be considered. Firstly, patients with AD

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