Hi everyone! I was interested to read this opinion piece recently (featuring a quote from the MJFF chief scientist, too!):
https://www.science.org/content/article/most-dementia-patients-have-multiple-brain-diseases-how-should-they-be-treated
My basic summary is that the labels of Parkinson’s, Alzheimer’s, and other brain diseases associated with older age are not super useful, because many people exhibit symptoms of multiple diseases. Instead of developing therapeutics for each disease, we might see more success in treating biomarkers such as dysregulated beta amyloid, tau, and alpha synuclein, which might then lead to reduction of symptoms currently labelled as PD or AD, etc.
On the one hand, it makes sense to try to address biomarkers which associate with poorer outcomes, and a patient is perhaps less concerned about whether their cognitive decline is due to PD or AD, as compared to halting that decline. But I’m aware that the new AD drugs start from just this premise, and have largely failed to meet efficacy endpoints (or displayed only modest results for the patient’s daily life, even if biomarkers “improve”). So I’m not sure that “treating” tau or asyn, even together, is the silver bullet the field is looking for.
What do others think? Am I missing a part of the argument where the biomarker-focused approach has more potential that I’m just not seeing? Is the thinking that the main damage is caused by the double (or triple) deficit of well-regulated asyn, tau, or a-beta together, triggering a worse outcome? I’m also interested in where Dementia with Lewy Bodies fits into this spectrum of brain diseases, as it somewhat bridges a gap between PD and AD, but is still considered a separate diagnosis. Your thoughts would be appreciated!
This is a wonderful submission. I think the article highlights an important point in how we view neurodegenerative diseases (though viewed completely as separate disorders, conditions like PD, AD, and DLB often overlap biologically, with many patients showing mixed pathologies involving alpha-synuclein, tau, amyloid-beta, inflammation, and vascular changes).
That said, I also share the concern that targeting biomarkers alone may not be enough, since recent anti-amyloid therapies have shown that improving biomarkers does not always translate into major clinical benefit. It may be that the real problem is the interaction among these pathologies. For instance, there is growing evidence of cross-seeding phenomena (alpha-synuclein promoting tau aggregation, tau facilitating amyloid toxicity, inflammatory signaling amplifying all three). So the “double-hit” or “triple-hit” hypothesis you mentioned may indeed be closer to reality than a single-protein model.
DLB is also particularly interesting because it sits at the intersection of PD and AD, often showing overlapping clinical and pathological features, which supports the idea of a disease spectrum. Still, I think clinical diagnoses remain useful for predicting symptoms and guiding treatment, even as the field moves toward more biology-centered and potentially combination-based therapeutic approaches.
Thanks for your perspective! I hadn’t thought about the potential for cross-seeding, but this makes a lot of sense to me. In which case, each dysregulated biomarker suggests greater risk of symptoms from this spectrum, even if we can’t measure a linear correlation between each biomarker and symptoms, as they might be putting the patient at greater risk by their combined effects.
I tend to agree that clinical diagnoses are still useful, not least for their social function of being a convenient way for patients and clinicians to talk about a diagnosis, prognosis, and treatment plan. We are still some distance away from practical treatment plans and drugs based on the biology-centred approach of addressing biomarkers. Therefore, the disease labels are our best tools for explaining the current understanding of symptoms and prognosis while research continues.
I appreciate your thoughts on this!