Accelerating Alzheimer's Research: Translucence Biosystems at the Alzheimer's Association International Conference® (AAIC24)

Translucence Biosystems recently presented at the Alzheimer's Association International Conference® (AAIC24) in Philadelphia. Co-Founder & CEO, Damian Wheeler, Ph.D., and expert Chase Redd shared our tools, technologies, and 3D histology techniques that are helping accelerate Alzheimer's research.

At the conference, Translucence Biosystems showcased two posters highlighting how tissue clearing and light sheet microscopy technologies are revolutionizing preclinical Alzheimer's disease research. The first, titled “Brain-Wide Cellular-Resolution Measurement of Antibody Therapeutic Biodistribution,” featured our collaborative work with Lundbeck. This study utilized tissue clearing and light sheet imaging to visualize the distribution and target engagement of antibody-based therapeutics designed to cross the blood-brain barrier (BBB).

In this study, we took advantage of a bispecific antibody engineered to bind to the Alzheimer’s Disease target, BACE1, and the transferrin receptor (TfR1), which facilitates shuttling the antibody across the brain endothelium and into the brain parenchyma by hijacking the mechanism that shuttles iron across the BBB. A group of mice were dosed with the bispecific antibody mentioned above, and another group was dosed with a monospecific anti-BACE1 antibody. Then, to visualize the brain-wide distribution of the IV-dosed antibody therapeutics, we performed our modified iDISCO-based clearing protocol and imaged the samples in ~25 min using our Mesoscale Imaging System and a Zeiss Z.1 Lightsheet.

To specifically measure the parenchymal levels of Ab therapeutic that have crossed the BBB, Translucence Biosystems developed an AI-powered workflow that segments and removes the blood vessels from the images, and we are integrating this vasculature subtraction into our regional quantification tool. These methods facilitate the brain-wide measurement of experimental antibody therapeutics crossing the blood-brain barrier and engaging their targets, which is vital for preclinical testing of novel Alzheimer's Disease antibody-based therapeutics.

The second poster, “Brain-Wide Cellular-Resolution Quantification of Amyloid Plaques and Microglia in AD Model Mice,” showcased how Translucence Biosystems' is applying its AI-powered 3TK software with iDISCO-based tissue clearing and light sheet microscopy, to produce anatomically precise mapping of β-amyloid deposition and neuroinflammation across whole mouse brains. These tools offer unbiased and valuable insights into the efficacy of therapies targeting these hallmarks of Alzheimer's disease.

In this study, Translucence Biosystems' AI-powered 3TK software is used to segment individual immunostained microglia and amyloid plaques throughout the brain in the 5xFAD mice. The 3TK AI-powered workflow can distinguish between β-amyloid in plaques and β-amyloid present in neuronal cell bodies to generate brain-wide measurements of both products in the same fluorescent channel.

For the measurement of neuroinflammation, Translucence Biosystems has also developed three AI-powered workflows, one to count microglia, one to measure microglial shape, and a third for the detection of plaque-associated microglia (PAM). The workflow used to identify plaque-associated microglia throughout the brain shows that PAM regional distribution is correlated with brain-wide measurements of β-amyloid plaques.

The research in these posters highlights how Translucence Biosystems is contributing to the acceleration of Alzheimer's research by developing tools and techniques that enable researchers to visualize and quantify brain-wide Alzheimer's Disease pathology in response to a wide variety of experimental treatments.

By combining 3D tissue clearing, light sheet microscopy, and AI-powered 3D quantification, Translucence Biosystems is enabling unbiased, brain-wide analysis of antibody therapeutics, β-amyloid, and neuroinflammation.

We are grateful to have participated in this year's AAIC conference and to share how advances in tissue clearing and light sheet microscopy can accelerate pre-clinical CNS therapeutic development and shape the future of Alzheimer's Disease research. Translucence Biosystems' goal is to provide researchers with the tools needed to make breakthroughs in understanding Alzheimer's disease and related disorders.

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This article mentions 3D Tissue Clearing, AI-Powered 3D Quantification, Alzheimer’s Disease, Neuroinflammatory Diseases, and Therapeutic Antibody Detection services. Visit our services page for a comprehensive list of our Custom Services and Full-Pipeline Services.

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