"Dementia, Tracked in Real Time with a 'Mini Brain'... New Path Opened for Early Alzheimer's Diagnosis [Reading Science]"

Non-Invasive Analysis Without Cerebrospinal Fluid or PET Scans
Raising Hopes for Securing the Treatment "Golden Time"

A technology that enables real-time observation of the progression of Alzheimer's disease—offering the potential for earlier diagnosis and treatment—has been developed by a Korean research team.

The research team led by Professor Heeho Park of the Department of Biotechnology at Korea University, in collaboration with Professor Bomi Kwon from Sejong University and Professor Honggi Yoo from KAIST, announced on April 20 that they have developed a non-invasive diagnostic platform for Alzheimer's disease utilizing brain organoids.

A visualized diagram of the entire process of the Alzheimer's disease brain organoid model and FLIM analysis platform built based on hiPSC. Provided by the research team

Alzheimer's disease is a representative neurodegenerative disorder affecting over 50 million people worldwide, with brain cell damage beginning 15 to 20 years before symptoms appear. However, current early diagnosis methods are limited, as they rely on burdensome procedures such as cerebrospinal fluid collection or expensive positron emission tomography (PET) scans.

Real-time Disease Progression Analysis Using a 'Mini Brain'

The research team recreated Alzheimer's disease by producing brain organoids based on human induced pluripotent stem cells (hiPSC) derived from patient cells. Organoids are 'mini organs' that mimic the structure and function of real organs through the cultivation of stem cells.

In particular, the team succeeded in precisely controlling the expression timing of the PSEN1 gene, a major genetic cause of familial Alzheimer's disease, thereby replicating the core pathological features of the disease in the 'mini brain.' This overcomes the limitations of existing cell and animal models, which could not fully reflect the complex structure of the human brain.

Research team photo. Top row from left: Heeho Park, Professor of Life Sciences at Korea University; Bomi Kwon, Professor of Mechanical and Aerospace Engineering at Sejong University; Hongki Yoo, Professor of Mechanical Engineering at KAIST (all corresponding authors). Bottom row from left: Jihyun Kang, Integrated Master's and Doctoral Program student at Korea University; Boram Son, Professor at Kookmin University; Jeongmu Han, Postdoctoral Researcher at KAIST (all first authors). Provided by Korea University.

Furthermore, by combining multimodal fluorescence lifetime imaging microscopy (FLIM) technology, they established a three-dimensional profiling platform capable of real-time analysis of the metabolic state of living brain tissue. This platform can distinguish diseases and track disease progression by analyzing the fluorescence signals of intracellular metabolites without the need for additional staining.

Using this technology, the research team succeeded in distinguishing Alzheimer's disease and observing its progression in real time through a non-destructive method that does not damage tissue.

Professor Heeho Park stated, "We have developed a technology that enables non-invasive tracking of metabolic changes in Alzheimer's disease within living human brain organoids. In the future, we plan to expand this to cover sporadic Alzheimer's disease, aiming for precision diagnosis and the development of therapeutic strategies."

This research was published online in the March 11 edition of Nano Today, an international journal in the field of nanoscience (impact factor 10.9).

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