Evaluation of [125I]α-Bungarotoxin Binding to α7 Nicotinic Acetylcholinergic Receptors in Hippocampus–Subiculum of Postmortem Human Alzheimer’s Disease Brain
Year: 2025
Type: article
Study design: Observational Study
Abstract: Background/Objectives: 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 [125I]α-Bungarotoxin ([125I]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. Methods: For comparisons with common AD biomarkers, adjacent slices were anti-Aβ and anti-Tau immunostained for analysis using QuPath. Results: The [125I]α-Bgtx average SUB/HP ratio was 0.5 among the CN subjects, suggesting higher [125I]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 [125I]α-Bgtx binding in the AD subjects as the age increased. The Braak stage comparisons of [125I]α-Bgtx were made with [18F]flotaza binding to Aβ plaques and [125I]IPPI binding to Tau. A positive correlation was found between [125I]α-Bgtx and [18F]flotaza and there was a negative correlation between [125I]α-Bgtx and [125I]IPPI, implicating intricate relationships between the different AD biomarkers. Conclusions: [125I]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.
Source: Receptors
Authors: Allyson Ngo, Fariha Karim, Oshini V. Keerthisinghe, Tram B. Danh, Christopher Liang, Jogeshwar Mukherjee
Institution: University of California, Irvine
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,207
Awards: Novel Tau-Targeted Radiohalogenated Agents for Alzheimer's Disease, PET Imaging Agents for a4b2 Nicotinic Receptors, Evaluation of Monoamine Oxidase-A as a New Biomarker for Alzheimer's Disease, Arizona Alzheimer's Disease Core Center, G7125897906, National Brain and Tissue Resource for Parkinson's Disease and Related Disorders, PET Imaging agents for a4b2 Nicotinic Receptors, G8532964066, G9000083572
OpenAlex ID: W4408660975