4 research outputs found
Development of a Novel Ligand, [<sup>11</sup>C]TGN-020, for Aquaporin 4 Positron Emission Tomography Imaging
Aquaporin 4 (AQP4), the most abundant isozyme of the water specific membrane transporter aquaporin family, has now been implicated to play a significant role in the pathogenesis of various disease processes of the nervous system from epilepsy to Alzheimer’s disease. Considering its clinical relevance, it is highly desirable to develop a noninvasive method for the quantitative analysis of AQP distribution in humans under clinical settings. Currently, the method of choice for such diagnostic examinations continues to be positron emission tomography (PET). Here, we report the successful development of a PET ligand for AQP4 imaging based on TGN-020, a potent AQP4 inhibitor developed previously in our laboratory. Utilizing [<sup>11</sup>C]-TGN-020, PET images were successfully generated in wild type and AQP4 null mice, providing a basis for future evaluation regarding its suitability for clinical studies
Reduced CSF Water Influx in Alzheimer’s Disease Supporting the β-Amyloid Clearance Hypothesis
<div><p>Objective</p><p>To investigate whether water influx into cerebrospinal fluid (CSF) space is reduced in Alzheimer’s patients as previously shown in the transgenic mouse model for Alzheimer’s disease.</p><p>Methods</p><p>Ten normal young volunteers (young control, 21-30 years old), ten normal senior volunteers (senior control, 60-78 years old, MMSE ≥ 29), and ten Alzheimer’s disease (AD) patients (study group, 59-84 years old, MMSE: 13-19) participated in this study. All AD patients were diagnosed by neurologists specializing in dementia based on DSM-IV criteria. CSF dynamics were analyzed using positron emission tomography (PET) following an intravenous injection of 1,000 MBq [<sup>15</sup>O]H<sub>2</sub>O synthesized on-line.</p><p>Results</p><p>Water influx into CSF space in AD patients, expressed as influx ratio, (0.755 ± 0.089) was significantly reduced compared to young controls (1.357 ± 0.185; p < 0.001) and also compared to normal senior controls (0.981 ± 0.253, p < 0.05). Influx ratio in normal senior controls was significantly reduced compared to young controls (p < 0.01).</p><p>Conclusion</p><p>Water influx into the CSF is significantly reduced in AD patients. β-amyloid clearance has been shown to be dependent on interstitial flow and CSF production. The current study indicates that reduction in water influx into the CSF may disturb the clearance rate of β-amyloid, and therefore be linked to the pathogenesis of AD.</p><p>Trial Registration</p><p>UMIN Clinical Trials Registry <a href="https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&recptno=R000013940&type=summary&language=E" target="_blank">UMIN000011939</a></p></div
Schematic presentation of the results with mean (circle) and standard deviation (bar).
<p>Water influx into CSF space is expressed as influx ratio (IR): the ratio between the standardized uptake value (SUV, g/ml) of the ventricle to that of cortex. IR in Alzheimer’s disease patients (AD) is significantly reduced compared to both young controls (p < 0.001) and senior controls (p < 0.05), Mann-Whitney-Wilcoxon rank sum test. Note that there is no overlap in data points between AD and young controls. Reduction of influx ratio in senior controls compared to that in young control is found to be significant (p < 0.01) as well. A large range of influx ratio in senior controls suggests that the observed reduction likely represents one of the aging processes.</p
Consort Flow Diagram providing details of participant enrolment.
<p>Consort Flow Diagram providing details of participant enrolment.</p