Selective In Vitro and Ex Vivo Staining of Brain Neurofibrillary Tangles and Amyloid Plaques by Novel Ethylene Ethynylene-Based Optical Sensors

Florencia A Monge; Adeline M Fanni; Patrick L Donabedian; Jonathan Hulse; Nicole M Maphis; Shanya Jiang; Tia N Donaldson; Benjamin J Clark; David G Whitten; Kiran Bhaskar; Eva Y Chi

doi:10.3390/bios13020151

Selective In Vitro and Ex Vivo Staining of Brain Neurofibrillary Tangles and Amyloid Plaques by Novel Ethylene Ethynylene-Based Optical Sensors

Biosensors (Basel). 2023 Jan 18;13(2):151. doi: 10.3390/bios13020151.

Authors

Florencia A Monge^{1

2}, Adeline M Fanni^{1

2}, Patrick L Donabedian^{2

3}, Jonathan Hulse⁴, Nicole M Maphis^{4

5}, Shanya Jiang^{5

6}, Tia N Donaldson⁷, Benjamin J Clark⁷, David G Whitten^{2

8}, Kiran Bhaskar⁵, Eva Y Chi^{2

7}

Affiliations

¹ Biomedical Engineering Graduate Program, University of New Mexico, Albuquerque, NM 87131, USA.
² Center for Biomedical Engineering, University of New Mexico, Albuquerque, NM 87131, USA.
³ Nanoscience and Microsystems Engineering Graduate Program, University of New Mexico, Albuquerque, NM 87131, USA.
⁴ Molecular Genetics and Microbiology, University of New Mexico, Albuquerque, NM 87131, USA.
⁵ Department of Neuroscience, University of New Mexico, Albuquerque, NM 87131, USA.
⁶ Sartorius, Bohemia, NY 11716, USA.
⁷ Department of Psychology, University of New Mexico, Albuquerque, NM 87131, USA.
⁸ Department of Chemical and Biological Engineering, University of New Mexico, Albuquerque, NM 87131, USA.

Abstract

The identification of protein aggregates as biomarkers for neurodegeneration is an area of interest for disease diagnosis and treatment development. In this work, we present novel super luminescent conjugated polyelectrolyte molecules as ex vivo sensors for tau-paired helical filaments (PHFs) and amyloid-β (Aβ) plaques. We evaluated the use of two oligo-p-phenylene ethynylenes (OPEs), anionic OPE₁^2- and cationic OPE₂⁴⁺, as stains for fibrillar protein pathology in brain sections of transgenic mouse (rTg4510) and rat (TgF344-AD) models of Alzheimer's disease (AD) tauopathy, and post-mortem brain sections from human frontotemporal dementia (FTD). OPE₁^2- displayed selectivity for PHFs in fluorimetry assays and strong staining of neurofibrillary tangles (NFTs) in mouse and human brain tissue sections, while OPE₂⁴⁺ stained both NFTs and Aβ plaques. Both OPEs stained the brain sections with limited background or non-specific staining. This novel family of sensors outperformed the gold-standard dye Thioflavin T in sensing capacities and co-stained with conventional phosphorylated tau (AT180) and Aβ (4G8) antibodies. As the OPEs readily bind protein amyloids in vitro and ex vivo, they are selective and rapid tools for identifying proteopathic inclusions relevant to AD. Such OPEs can be useful in understanding pathogenesis and in creating in vivo diagnostically relevant detection tools for neurodegenerative diseases.

Keywords: amyloid plaques; biosensors; dyes; fluorescence imaging; neurofibrillary tangles; optical imaging; paired helical filaments; tau.

MeSH terms

Alzheimer Disease* / diagnosis
Amyloid beta-Peptides
Animals
Brain / metabolism
Ethylenes / metabolism
Humans
Mice
Neurofibrillary Tangles* / metabolism
Neurofibrillary Tangles* / pathology
Plaque, Amyloid
Rats
Staining and Labeling
tau Proteins

Substances

tau Proteins
Amyloid beta-Peptides
Ethylenes

Abstract

MeSH terms

Substances

Grants and funding