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Measurement of Aβ Amyloid Plaques and Tau Protein in Postmortem Human Alzheimer’s Disease Brain by Autoradiography Using [18F]Flotaza, [125I]IBETA, [124/125I]IPPI and Immunohistochemistry Analysis Using QuPath

Authors :
Rommani Mondal
Yasmin K. Sandhu
Vallabhi M. Kamalia
Brooke A. Delaney
Amina U. Syed
Grace A. H. Nguyen
Taylor R. Moran
Roz R. Limpengco
Christopher Liang
Jogeshwar Mukherjee
Source :
Biomedicines, Vol 11, Iss 4, p 1033 (2023)
Publication Year :
2023
Publisher :
MDPI AG, 2023.

Abstract

High-resolution scans of immunohistochemical (IHC) stains of Alzheimer’s disease (AD) brain slices and radioligand autoradiography both provide information about the distribution of Aβ plaques and Tau, the two common proteinopathies in AD. Accurate assessment of the amount and regional location of Aβ plaques and Tau is essential to understand the progression of AD pathology. Our goal was to develop a quantitative method for the analysis of IHC–autoradiography images. Postmortem anterior cingulate (AC) and corpus callosum (CC) from AD and control (CN) subjects were IHC stained with anti-Aβ for Aβ plaques and autoradiography with [18F]flotaza and [125I]IBETA for Aβ plaques. For Tau, [124I]IPPI, a new radiotracer, was synthesized and evaluated in the AD brain. For Tau imaging, brain slices were IHC stained with anti-Tau and autoradiography using [125I]IPPI and [124I]IPPI. Annotations for Aβ plaques and Tau using QuPath for training and pixel classifiers were generated to measure the percent of the area of Aβ plaques and Tau in each slice. The binding of [124I]IPPI was observed in all AD brains with an AC/CC ratio > 10. Selectivity to Tau was shown by blocking [124I]IPPI with MK-6240. Percent positivity for Aβ plaques was 4–15%, and for Tau, it was 1.3 to 35%. All IHC Aβ plaque-positive subjects showed [18F]flotaza and [125I]IBETA binding with a positive linear correlation (r2 > 0.45). Tau-positive subjects showed [124/125I]IPPI binding with a stronger positive linear correlation (r2 > 0.80). This quantitative IHC–autoradiography approach provides an accurate measurement of Aβ plaques and Tau within and across subjects.

Details

Language :
English
ISSN :
22279059
Volume :
11
Issue :
4
Database :
Directory of Open Access Journals
Journal :
Biomedicines
Publication Type :
Academic Journal
Accession number :
edsdoj.8a6befdfb1ae450b87d26ce84809c546
Document Type :
article
Full Text :
https://doi.org/10.3390/biomedicines11041033