AD/PD 2022 | Revising the amyloid hypothesis in Alzheimer’s disease: the probabilistic model

In a few words, what we have developed is a new way to see, to conceptualize the disease. Now, the disease is conceptualized as a chain of events, starting from amyloid, going on tau, then to neurodegeneration, and then to symptoms. It’s a deterministic chain of events. You start with amyloid, you end up with the clinical symptoms. It’s very simple, very easy to understand.

Problem is, it doesn’t fit the data. Because what the data suggests is that in autosomal dominant Alzheimer’s disease, this is the case. This chain of events fits autosomal dominant, but 99.9 something percent of cases are not autosomal dominant. They’re sporadic, and in sporadic Alzheimer’s disease, what happens is that you have amyloid. Sometimes you have tau. Sometimes you have neurodegeneration. Sometimes you have symptoms.

So in the end, it’s a probabilistic chain of events. It’s not deterministic. This has a number of implications in terms of diagnosis, in terms of prevention, in terms of drug development, in terms of research. It changes the way we see the disease. It’s sort of a relativistic theory of Alzheimer’s disease.

When the theory of relativity was developed, there was not an immediate impact on daily life, on the way men looked at the world. But the impact could be felt in the following decades, following the impact, say, on technological and scientific thinking that followed the theory of relativity.

With all due respect for the theory of relativity, but we believe this is a sort of change of a perspective, change of attitude, change of thinking, a way of thinking to the disease that is a sort of a theory of relativity for Alzheimer’s disease.