Evaluation of [<sup>125</sup>I]α-Bungarotoxin Binding to α7 Nicotinic Acetylcholinergic Receptors in Hippocampus–Subiculum of Postmortem Human Alzheimer’s Disease Brain
<b>Background/Objectives:</b> Alzheimer’s disease (AD) severely hinders cognitive function in the hippocampus (HP) and subiculum (SUB), impacting the expression of nicotinic acetylcholine receptors (nAChRs) such as the α7-subtype. To investigate α7 nAChRs as a potential PET imaging bioma...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-03-01
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| Series: | Receptors |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2813-2564/4/1/7 |
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| Summary: | <b>Background/Objectives:</b> Alzheimer’s disease (AD) severely hinders cognitive function in the hippocampus (HP) and subiculum (SUB), impacting the expression of nicotinic acetylcholine receptors (nAChRs) such as the α7-subtype. To investigate α7 nAChRs as a potential PET imaging biomarker, we report the quantitative binding of [<sup>125</sup>I]α-Bungarotoxin ([<sup>125</sup>I]α-Bgtx) for binding to postmortem human AD (n = 29; 13 males, 16 females) HP compared to cognitively normal (CN) (n = 28; 13 male, 15 female) HP. <b>Methods:</b> For comparisons with common AD biomarkers, adjacent slices were anti-Aβ and anti-Tau immunostained for analysis using QuPath. <b>Results:</b> The [<sup>125</sup>I]α-Bgtx average SUB/HP ratio was 0.5 among the CN subjects, suggesting higher [<sup>125</sup>I]α-Bgtx binding in the HP gray matter regions. The AD subjects showed overall less binding than the CN subjects, with no statistical significance. A positive correlation was found in the [<sup>125</sup>I]α-Bgtx binding in the AD subjects as the age increased. The Braak stage comparisons of [<sup>125</sup>I]α-Bgtx were made with [<sup>18</sup>F]flotaza binding to Aβ plaques and [<sup>125</sup>I]IPPI binding to Tau. A positive correlation was found between [<sup>125</sup>I]α-Bgtx and [<sup>18</sup>F]flotaza and there was a negative correlation between [<sup>125</sup>I]α-Bgtx and [<sup>125</sup>I]IPPI, implicating intricate relationships between the different AD biomarkers. <b>Conclusions:</b> [<sup>125</sup>I]α-Bgtx shows complimentary potential as a α7 nAChR imaging agent but needs more preclinical assessments to confirm effectiveness for translational PET studies using α7 nAChR radioligands. |
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| ISSN: | 2813-2564 |