A new study by members of the Translational Neuroimaging Laboratory at the McGill Research Centre for Studies in Aging describes a new Alzheimer’s staging system they devised to help clinicians stage the disease and come up with targeted care plans for their patients. We spoke to lead author Joseph Therriault, a PhD student in the lab of Pedro Rosa-Neto, MD, PhD, the Centre’s Director and an Associate Professor in the Departments of Neurology and Neurosurgery and Psychiatry at McGill, about the implications of their study, recently published in Nature Aging.
Can you tell us what’s new in this paper?
Currently, Alzheimer’s disease is officially diagnosed with an autopsy. These autopsies use staging systems to determine the severity of Alzheimer’s disease. In particular, these staging systems are heavily based on a framework called Braak staging. We took the Braak staging system and applied it to living people using high-affinity tau-PET imaging.
How does it add to what was already known about Alzheimer’s?
This allows us to understand how gold-standard assessments of Alzheimer’s relate to emerging biomarkers, which can only be assessed in living people. It also allows us to use the staging system to understand the natural history of Alzheimer’s disease. Basically, our paper provides a new way to think about the disease, how it progresses, and who will respond to treatment.
Where did the idea of a new staging system come from?
My colleague Tharick Pascoal, a former PhD student in Dr. Rosa-Neto’s lab who is now a professor in Pittsburgh, developed the application of the staging system to living people over the course of the last two years. I had the idea to use the staging system to model the natural history of Alzheimer’s disease. Once we got started, the paper moved very quickly.
Can your findings help with early intervention of Alzheimer’s?
Recently, the understanding of Alzheimer’s disease has totally transformed. The disease used to be considered a memory disorder that progressively got worse and worse. Recently, the disease has been re-defined based on it’s biological features. This allows the disease to be identified in people who have specific pathological changes, but do not yet have symptoms. We think targeting the disease in the preclinical phase is the best chance of success. So essentially, we took the ideas of the biological definition and tried to stage the biological abnormalities we see in Alzheimer’s, using PET scans.
Why is staging so important in Alzheimer’s disease?
Staging of disease severity is an important part of almost all areas of medicine. Our paper brings Alzheimer’s disease closer to the area of personalized medicine and targeted interventions. Disease staging could also be used in clinical trials to ensure that different patients are in a similar phase of their disease.
Where do you think this will lead, in terms of Alzheimer’s diagnosis and care?
For now, molecular imaging of Alzheimer’s disease neuropathology is limited to highly specialized academic centres. However, we can imaging a not-so-distant future in which PET imaging is used to help understand the cause of cognitive impairment (ie, is it Alzheimer’s, or is it something else?) in addition to helping doctors understand how severe the disease is, and what this indicates for the patient’s future.
Do you have any unanswered questions about this system?
An important area of debate in our field is whether everyone fits into the Braak system, or whether there is deviation from it. We are continuing research to see how this system can be meaningfully applied to everyone.
Anything else you’d like to add?
I’d like to thank my supervisor, Dr Pedro Rosa-Neto, who made all this work possible.
Therriault, J., Pascoal, T.A., Lussier, F.Z. et al. Biomarker modeling of Alzheimer’s disease using PET-based Braak staging. Nat Aging (2022). https://doi.org/10.1038/s43587-022-00204-0