Fused Cycloheptatriene-BODIPY Is a High-Performance Near-Infrared Probe to Image Tau Tangles

Area of Science:

• Neuroscience
• Biochemistry
• Medical Imaging

Background:

• Neurofibrillary tangles (NFTs) composed of hyperphosphorylated Tau are key hallmarks of Alzheimer's disease and tauopathies.
• Current fluorescent probes lack specificity, hindering accurate diagnosis by failing to distinguish NFTs from β-amyloid plaques.

Purpose of the Study:

• To develop a novel near-infrared (NIR) imaging probe with high affinity and specificity for NFTs.
• To evaluate the probe's ability to cross the blood-brain barrier and detect tauopathy in vivo.

Main Methods:

• Development of a fused cycloheptatriene-BODIPY derivative (TNIR7-1A).
• In vitro and in vivo NIR fluorescence imaging in transgenic tauopathy mouse models (rTg4510).
• Ex vivo fluorescence staining and molecular docking studies.

Main Results:

• TNIR7-1A demonstrated high affinity and specificity for NFTs in vitro.
• The probe successfully penetrated the blood-brain barrier and enabled clear in vivo visualization of tauopathy.
• Ex vivo analysis confirmed high sensitivity and specificity, with molecular docking revealing hydrophobic interactions with NFTs.

Conclusions:

• TNIR7-1A is a high-performance probe for selective detection of neurofibrillary tangles.
• The probe shows significant potential for diagnosing Alzheimer's disease and other tauopathies.
• NIR imaging with TNIR7-1A offers an improved method for in vitro and in vivo tauopathy detection.