11C-DASB shows serotonergic alterations in Alzheimers patients

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In addition to the progressive memory and cognitive deterioration that are the hallmarks of Alzheimer’s disease (AD), psychological problems such as depression and hallucinations are also common. A team of Japanese researchers recently conducted molecular imaging in early- to moderate-stage AD patients and found evidence that preclinical depression may be a pathophysiologic feature of the disease, according to results published in the August issue of the Journal of Nuclear Medicine.

“We examined in vivo changes in the brain serotoninergic system and glucose metabolism by scanning early- to moderate-stage AD patients with and without depression using PET with a radiotracer for the serotonin transporter, 11C-3-amino-4-(2-dimethylaminomethylphenylsulfanyl) benzonitrile (DASB), and a metabolic marker, 18F-FDG,” the authors wrote.

Scientists from the Hamamatsu University School of Medicine in Hamamatsu, Japan, enrolled 15 AD patients (seven manifesting depression and eight non-depressed) who had not taken antipsychotic medication and 10 age-, sex- and education-matched healthy control subjects in the study.

Representative PET image of 11C-DASB binding relative to cerebellar uptake in a depressive Alzheimer’s patient. AD-d=depressive AD. Image and caption courtesy of SNM.

All participants first underwent a 3D MRI scan (0.3T MRP7000AD, Hitachi Medical Systems) just before the PET study. The PET exams were performed on a high-resolution brain SHR12000 tomograph (Hamamatsu Photonics). Quantitative 11C-DASB PET measurements were conducted on all study participants followed by 18F-FDG PET scans in the AD group. The MRI scan was used by the researchers to determine the brain areas for setting the regions of interest (ROIs).

“The MRI measurements and a mobile PET gantry allowed us to reconstruct PET images parallel to the intercommisural line without reslicing,” the authors wrote. “Using this approach, we were able to allocate ROIs to the target regions of the original PET images.”

The team used region-of-interest (ROI) analysis to examine changes in 11C-DASB binding potential in the serotonergic projection region (striatum). In addition, statistical parametric mapping was used to examine whether glucose metabolism in any brain region correlated with levels of 11C-DASB binding in the dense serotonergic projection region in AD.

“Striatal 11C-DASB binding was significantly lower in AD patients, irrespective of depression, than in healthy controls, and 11C-DASB binding in other dense projection areas decreased significantly in the depressive group, compared with the control group,” the authors wrote.

The researchers also determined that the 11C-DASB binding potential levels in the subcortical serotonergic projection region correlated negatively with the depression score but not with the dementia score. Thus, the study found no significant correlation between presynaptic dysfunction in the subcortical serotonergic projection region and dementia.

In addition, statistical parametric mapping correlation analysis showed that glucose metabolism in the right dorsolateral prefrontal cortex was positively associated with the level of striatal 11C-DASB binding in AD, according to the scientists.

Although the study cohort was small, the investigators believe that their results show serotoninergic system changes occur as a result of AD.

“A significant reduction in 11C-DASB binding in non-depressed AD patients suggests that presynaptic serotonergic function is altered before the development of psychiatric problems such as depression in AD,” they wrote. “The depressive AD group showed greater and broader reductions in binding, suggesting that a greater loss of serotonergic function relates to more severe psychiatric symptoms in the disease.”