A person will have Alzheimer's years before ever knowing it. The disorientating erasure of memories, language, thoughts — in essence, all that makes up one's unique sense of self — is the final act of this enigmatic disease that spends decades disrupting vital processes and dismantling the brain's delicate structure.
Once symptoms surface and doctors make a diagnosis, though, it can often be too late. Damage is widespread, impossible to reverse. No cure exists.
Attempts to develop drugs that clear away toxic accumulations of amyloid-beta and tau proteins — hallmarks of the disease that cause neurons to die — have ended in hundreds of failed clinical trials. Today, some scientists are skeptical over whether removing amyloid plaques is even enough. Others have a hunch that the best line of attack won't target just one aspect of the disease, but many of them, all at once.
Tomás R. Guilarte, who leads a brain health research group at FIU, is looking at one of those targets: TSPO. It may not only be among the earliest Alzheimer's biomarkers — detectable before memory loss or cognitive decline — but a promising pathway to thwart chronic, damaging inflammation, according to the team's latest study published in top neurology journal Acta Neuropathologica.
"Neuroinflammation is a very early event in Alzheimer's that influences its onset," says Guilarte, dean of FIU's Robert Stempel College of Public Health & Social Work.
"If we can use TSPO to detect it early, right at the beginning stages of the disease, it could mean slowing progression or delaying symptoms by five or six years. That's five or six years where someone has a better quality of life."
Normally, in the brain, TSPO (or translocator protein 18 kDa) is present at very low levels.
But when the brain's delicate balance is thrown off, like when there is neuroinflammation, it increases and keeps on increasing, Guilarte explains. And it keeps spreading and spreading.
On PET scans, it can look like the brain is on fire. TSPO shows up as a vivid red-orange hue.
Guilarte has a long history with TSPO — among a handful of scientists who helped validate it as a biomarker of neuroinflammation. This work started in the 1990s when he was at Johns Hopkins University. Now, clinicians and researchers at major medical centers around the world rely on TSPO to track neuroinflammation not only in neurodegenerative but neurological and psychiatric diseases.
This latest study provides a never-before-seen look at TSPO.
For the first time, with the help of state-of-the-art imaging technology, Guilarte's team was able to pinpoint where and when TSPO initially appears in the brain.
They found it coincides with the first appearance of small scatterings of amyloid plaques in the subiculum, part of the hippocampus, a brain structure critically important for learning and memory.
Then, they zoomed in to see what specific glial cells — including microglia and astrocytes, which are responsible for protecting neurons — were giving off the TSPO signals.
What you'll learn in this story
- TSPO, a key biomarker in neuroinflammation, could help detect Alzheimer's disease years before memory loss or other symptoms appear — potentially leading to advances in how the disease is diagnosed and treated, according to new research.
- TSPO levels first rise in the subiculum — a critical part of the hippocampus — as early as six weeks of age in a mouse model, roughly equivalent to age 18–20 in humans.
- Findings were confirmed using human brain tissue donated by members of the world's largest group of individuals with early-onset familial Alzheimer's, located in Antioquia, Colombia.
