Research Roundup - April 2025

Read the below Research Roundup from Penn FTD Center Research Assistant Professor Jeffrey Phillips PhD.

Terms to Know:

Positron emission tomography (PET): an imaging technique that uses mild radioactivity to image disease features in the brain or body. The radioactive element is attached to an antibody that will bind to whatever we want to image (e.g., clumps of toxic proteins in the brain).

Tau: a protein that normally helps form the “backbone” of brain cells, but that becomes misfolded in Alzheimer’s disease and clumps together into toxic tangles.

Amyloid-beta: a second toxic protein (along with tau) that is found in the brains of Alzheimer’s disease patients.

What we knew:

A newer PET tracer for the tau protein, named PI-2620, has been shown to bind well to tau in the brains of people with Alzheimer’s disease. Following standard methods in neurology research, we categorized people into those with Alzheimer’s disease vs. non-Alzheimer’s dementias (like frontotemporal dementia) based on whether or not they had amyloid-beta in their brain.

What we didn’t know:

There are relatively few studies investigating whether the PI-2620 tracer can help us distinguish between Alzheimer’s disease and non-Alzheimer’s dementias. There also aren’t many studies testing whether the PI-2620 signal is correlated with other markers of Alzheimer’s disease, such as new blood-based measures of tau and amyloid-beta.

What this research/study shows:

We found that PI-2620 signal in the medial temporal lobe, an area that is affected early in Alzheimer’s disease, effectively distinguished suspected Alzheimer’s disease from non-Alzheimer’s dementia cases. We also found that the PI-2620 signal was correlated with phospho-tau 217, a measure of the tau protein that is derived from blood plasma.

What to do with this information:

There is currently a lot of research on blood-based markers of Alzheimer’s disease and other dementias. If these measures prove as reliable as more costly and technically difficult methods like PET for diagnosis, they will likely become widely used by neurologists.

More Information:

We have previously published on blood-based disease markers and another tau PET tracer, flortaucipir: https://pmc.ncbi.nlm.nih.gov/articles/PMC11180939/

We have also shown that rare variants of Alzheimer’s disease who are impaired in other cognitive domains than memory have different patterns of tau pathology than typical Alzheimer’s cases: https://pmc.ncbi.nlm.nih.gov/articles/PMC9936795/.