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Both miss the whole picture, Jun said, creating a scientific reality akin to the old parable about the blind men and the elephant, in which the people in the story are asked to feel a particular part of the animal individually. They then each form an erroneous conclusion about the animal based on their limited and subjective knowledge.

Today, those scientific limits are lifting.

At SUNY Buffalo, Jun is using advanced scientific technology from Thermo Fisher Scientific, specifically the Thermo™ Scientific™ Orbitrap™ Astral™ Mass Spectrometer (MS), to study Alzheimer’s in a way that preserves spatial detail, allowing researchers to see where molecular changes occur, how they evolve from region to region, and how early disease begins to take hold.
 

Mass spectrometry is a technology that allows scientists to identify and measure molecules based on their mass. The Orbitrap Astral MS dramatically increases the sensitivity, speed, and accuracy with which scientists can analyze complex samples, Jun said.
 

“It’s revolutionary,” Jun said. “The Orbitrap Astral’s absolute sensitivity is at least 50 times higher than previously considered state-of-the-art. And it’s fivefold faster, reducing bottlenecks in the lab.  It really changes the game.”
 

Mapping the Alzheimer’s brain
 

The leap in mass spectrometry power allows Jun’s lab to analyze extremely small samples of brain tissue, detect low-abundance molecules, specifically proteins, and design experiments that were previously not viable.
 

Proteins are the focus because they are the molecules that perform most functions in living systems. They build and maintain cells, carry signals between cells, regulate the immune system, and determine whether disease advances or stalls. Proteomics, the large-scale study of proteins, offers a dynamic view of biology, capturing what is happening inside cells as disease unfolds.
 

For years, Alzheimer’s research focused on visible hallmarks such as plaques and neurofilament tangles, features that could be observed and measured reliably with available tools. But those markers often appear after the disease is well underway.
 

Jun’s work is aimed at what happens earlier, and where it happens.
 

Using the Orbitrap Astral MS, Jun and his team are creating whole-tissue spatial maps that show not just which proteins are present in brain tissue, but also exactly where they are located, and whether they are active or inactive as disease progresses over time.
 

“People didn’t know previously how Alzheimer’s-related proteins distribute in the brain,” Jun said. “And their localization is very important.”
 

His lab employs a 3D-printed micro-scaffold that looks like a honeycomb to divide a thin slice of brain tissue into hundreds of microscopic regions. Each region is analyzed separately, then reassembled computationally into a protein-distribution map.
 

Jun said the work would not be feasible without the Orbitrap Astral MS.
 

“It’s a critical enabling factor,” he said. “If Astral didn’t come out when it did, spatial mapping at this depth, sensitivity and accuracy would not be possible.”
 

More than 800 peer-reviewed scientific journal articles have cited the utility of the Orbitrap Astral MS since its introduction in 2023. Its increased capabilities have been recognized by leading scientists worldwide.

Using the system, Jun said his team can reliably map more than 10,000 proteins across whole brain tissue, roughly doubling what was previously achievable while maintaining accuracy and reproducibility.

Seeing activity, not just presence
 

Beyond knowing where proteins are, Jun’s team is also looking at what proteins are doing.
 

Proteins can change behavior when they are chemically modified through a process called phosphorylation, which can switch a protein’s activity on or off or alter what it does. These changes are critical in neurodegenerative disease.
 

This is especially evident for tau, a protein long associated with Alzheimer’s disease. Tau has hundreds of potential phosphorylation sites, but only a handful are known to be biologically meaningful.
 

With a new technique developed in Jun’s lab, the Orbitrap Astral MS enabled whole-tissue, in-depth mapping of more than 30,000 protein phosphorylation sites in the brain, showing the activation or inactivation status of key regulatory proteins. The lab’s mapping revealed that certain phosphorylated forms of tau appear only in specific brain regions - and often at very early stages of disease.
 

“People predicted some of these patterns,” Jun said. “But they only saw them at very late stages. This is much earlier, and much more sensitive than traditional methods.”
 

Impact on drug development
 

Those insights could have real consequences for drug development.
 

Jun pointed to past clinical failures involving targets that looked promising in genetic or bulk-tissue data but were never active in the right brain regions. Identifying those mismatches earlier could save drug developers many millions of dollars, he said.
 

With the findings from his lab added to previous research, 96 percent of the proteins that are predicted to play a role in Alzheimer’s have now been mapped, including many thought to be responsible for the disease, Jun said. He has submitted his lab’s findings for publication in a peer-reviewed journal.
 

“There are approximately 30,000 papers published on these proteins,” Jun said. “But protein distribution was never measured for most of them, because the technology didn’t exist. Now, for the first time, with Orbitrap Astral we know how they are distributed in the brain.
 

“This gives us totally new insights - another dimension of insight - into how Alzheimer’s disease pathways actually work,” he said.
 

Jun’s lab is applying the same approach to other diseases.
 

In diabetes research, his team developed a highly sensitive method to measure elusive insulin-related molecules. The work, which was featured on the cover of Analytical Chemistry, showed that previously undetectable forms of proinsulin, a precursor protein that evolves into insulin, could be accurately measured at part-per-trillion levels in blood.
 

The research compared proinsulin levels in people with Type 1 diabetes and healthy individuals, allowing the team to document disease progression. The Orbitrap Astral MS was used to confirm the findings.
 

“People were initially skeptical,” Jun said. “Without Astral, confirmation would have been totally hopeless.”
 

Across Alzheimer’s, diabetes, and other disease research, Jun sees a common theme emerging: moving beyond averages to see biology as it actually exists.
 

“It’s not just more data,” he said. “It’s the right data, in the right place.”