This spring, his team published a research article<\/a> on their findings in the Nature journal Molecular Psychiatry.<\/p>\n\n\n
![\"Dr.](\"https:\/\/vet.purdue.edu\/news\/wp-content\/uploads\/2025\/07\/25lab_151-copy-1024x683.jpg\")
A new tool for sporadic AD<\/strong><\/p>\n\n\n\n The lab\u2019s new tool is an organoid, an artificially grown mass of cells built from human pluripotent stem cells and mimicking the functions of an organ \u2013 in this case, the brain. This type of model is often called a \u201cbrain on a chip\u201d or \u201cmini-brains\u201d because it\u2019s a miniaturized laboratory system designed to mimic key aspects of the brain\u2019s structure and function. A complex 3D model<\/strong><\/p>\n\n\n\n The model includes four major brain cell types commonly affected in Alzheimer\u2019s \u2013 neurons (nerve cells), astrocytes (star-shaped cells that support and protect neurons), microglia (immune cells that protect the brain) and vascular cells (which help maintain the blood-brain barrier, regulate blood flow and coordinate neural activity). Promising results on multiple fronts<\/strong> A potential model for drug discovery<\/strong>
The researchers developed the tool specifically for studying sporadic Alzheimer\u2019s disease (sAD), which accounts for more than 95% of AD cases and has no clear genetic cause. Most existing research tools are based on familial Alzheimer\u2019s \u2013 a much rarer, inherited form of the disease.
While sporadic AD is the prevailing form of Alzheimer\u2019s, it\u2019s influenced by multiple factors, making it difficult to identify causes and patterns.
\u201cSporadic AD doesn\u2019t have a clear cause. There are no specific gene mutations,\u201d Dr. Xu says. \u201cIt\u2019s really hard to get an sAD model. That\u2019s what we wanted to do here in this study.\u201d<\/p>\n\n\n\n
Putting all these brain cells together into a single 3D model can provide a clearer picture of how Alzheimer\u2019s disease affects the brain, says PhD student and lead author Yanru Ji.
\u201cIt\u2019s really hard for a single organoid to incorporate multiple different cell types and mimic AD-related pathologies at the same time,\u201d Ji says. \u201cThat\u2019s what we did here \u2013 incorporate all four different cell types. This helps us better mimic the brain environment.\u201d
Ji is passionate about neuroscience and wants to pursue a career in academia. She read several of Dr. Xu\u2019s publications while looking into graduate programs. Ji says she was drawn to the complexity and unknowns surrounding Alzheimer\u2019s disease, along with the opportunity to participate in his lab\u2019s novel research approaches.<\/p>\n\n\n\n
The researchers tested how well the model mimicked the development of Alzheimer\u2019s in humans and how effective it might be in validating new drugs under development. Results on both fronts were promising.
First, the team exposed the laboratory model to brain extracts from postmortem tissues of individuals with sporadic Alzheimer\u2019s. Within just four weeks, the models developed hallmark features of the disease. They included beta amyloid plaque-like buildup (abnormal clumps of protein fragments that disrupt neural function), tau tangles (twisted fibers of tau protein building up inside neurons), brain inflammation, synaptic loss (deterioration and disappearance of connections between neurons) and impaired neural activity.
Given that the model showed these signs of disease so quickly and strongly, the researchers believe it could be a very efficient tool for studying Alzheimer’s.
While longer culturing times might better reflect aging, Ji says that they were able to induce complex pathology in a short timeframe. Their results suggest that the model can efficiently reproduce key features of the aging brain, even in its current form.<\/p>\n\n\n\n
Next, the team looked at the model\u2019s potential for validating new Alzheimer\u2019s drugs by testing it with lecanemab. Created by Eisai Co., Ltd.; Biogen Inc.; and BioArctic , the drug has been approved by the FDA and is available in the marketplace. It targets beta amyloid, which are believed to damage brain cells and disrupt communication between neurons in people with Alzheimer\u2019s disease.
The medication reduced amyloid levels in the model while also increasing vascular inflammation, closely mirroring human responses.
\u201cThis was one of the things we wanted to try with this model,\u201d Ji says. \u201cWe want to build a human, physiologically relevant model for testing.\u201d
While the model is still being refined, Dr. Xu says it shows great promise for evaluating new treatments earlier and more effectively. He has applied for a patent via Purdue Research Foundation.<\/p>\n\n\n\n![\"Xu](\"https:\/\/vet.purdue.edu\/news\/wp-content\/uploads\/2025\/07\/25lab_220-1024x755.jpg\")