Grad student took lead on study that generated Alzheimer’s discovery

Cats and dogs with all manner of ailments used to visit then-vet student Daniel Martinez-Perez at an animal clinic in his hometown of Medellín, Colombia. The ones with dementia interested him most.

Telltale signs of the disease, as described by concerned pet owners, included nighttime pacing, getting lost and random vocalizing. Whereas Martinez-Perez could treat most other problems, the neurological disorder left him stumped. Beyond prescribing meds to ease symptoms, he could offer nothing more.

Moved by an inability to help his four-legged patients, he also recognized that their cognitive decline appeared not unlike what people with neurodegenerative conditions experience.

“Every animal is different, every species is different,” Martinez-Perez says, lumping homo sapiens into his analysis, “but the basic things, the biology and physiology, are pretty similar.”

Gnawing curiosity

His growing interest in early intervention for domesticated creatures soon expanded to include human beings. That spark led him to the world-renowned Alzheimer’s research group at the same school at which he was pursuing a veterinary degree, the University of Antioquia.

The neuroscientists there agreed to let him work in a lab and sit in on scientific discussions.

“At the beginning, I couldn't understand anything because I came from a clinical background,” Martinez-Perez recalls. “They were talking about molecules and things like that. I was just like, ‘ugh.’ I felt lost.

“But then I started getting things,” he says of his growing knowledge.

“Get it” he most certainly did. Martinez-Perez eventually applied to the university for a master’s in biomedical sciences focused on neuroscience and even put his newfound training in molecular processes to use as an assistant lecturer in the same veterinary program from which he had just earned a degree.

A year later, the dean of FIU’s Robert Stempel College of Public Health & Social Work came to town to establish a collaboration, and Martinez-Perez learned about opportunities in Miami. An acclaimed brain health and neurotoxicology researcher, Tomás R. Guilarte eventually offered the young man a fellowship and invited him into a Ph.D. program and his lab.

A blockbuster moment

Five years on, the pairing of mentor and grad student has paid off in spectacular fashion. Martinez-Perez served as lead author on a recently published paper that details a groundbreaking Alzheimer’s study led by Guilarte. It appears in the peer-reviewed journal Acta Neuropathologica.

The investigative team made an incremental scientific contribution with potentially huge ramifications. They zeroed in on a protein (TSPO) in the brain’s immune cells that Guilarte had previously discovered can serve as a biomarker of inflammation when “activated” and present at certain levels.

The new research answers specific questions about the protein – the where, when and why – en route to possibly developing a means for earlier detection of the disease and even treatment.

The much-heralded triumph confirms the collaborative power of a brilliant seasoned researcher and the drive and commitment of one just starting his career.

“He was really amazing,” Guilarte says of Martinez-Perez. While the two conferred regularly about how best to proceed, “He really took the bull by the horns, and he’s still doing that,” Guilarte asserts. “I guided him, and we discussed many points and what to do and what approach to take and so on and so forth, but he definitely took it upon himself. And he did the majority of the work.”

Unwavering dedication

To a casual observer, the steps to arriving at impactful results appear near-stupefying in their variety.

Martinez-Perez began by taking charge of devising and running an experiment to determine that test subjects - genetically engineered mouse models - had definitively developed Alzheimer’s. To ascertain the latter, he trained both test and control subjects to locate a burrow hole within a confined space and timed them on subsequent searches for the target; animals with the disease eventually lost the ability to achieve the goal.

He then prepared slides of brain tissue and applied stains and chemical reagents to highlight specific components and reactions. The latter would help make clear, for example, how many of the brain’s immune cells had attached themselves to the “sticky clumps,” or beta-amyloid plaques, that are the hallmark of Alzheimer’s. 

Relying on AI and machine learning tools, he then taught a software program how to distinguish immune cells from plaques to extract relevant data, including the amount of contact between them. With direction from the biostatistician on the team, he and the others then analyzed the generated information and compared their findings with human brain tissue, samples of which came from the neuroscience group of Antioquia.

Their discovery: a positive correlation between the level of activated protein in the brain and the number of immune cells directly touching plaques.

The breakthrough moves science a bit closer to cracking the code on what is typically a horrifying life sentence by proving an association between the protein and progression of the disease. An estimated 13 million Americans will have the debilitating disorder by 2050.

The future

For an early-career researcher, the chance to play a role in the long game that is the search for Alzheimer’s treatment has been exciting. Even with the goal still years if not decades away from realization, Martinez-Perez, 33, remains undaunted.

“That's something beautiful about science,” he says, “that every finding, at the end, opens a door for more questions. That's how science works.”

More investigations will follow. Guilarte already has ideas around using the latest results to develop a blood-based test that could screen for the disease. “Obviously, this is in its infancy,” he says.

In the short term, Martinez-Perez this month returns to Colombia not only to visit his mother but to present the lab’s celebrated findings at the Global Health Conference of the Americas in Cartagena. There he will cross paths with some of the very researchers who at one time welcomed him into their group. They belong to the global community of dedicated neuroscientists directing their genius toward ridding the world of a growing scourge.

And he is one of them.