I increasingly believe that the consistently negative results of clinical trials in most degenerative diseases are not because these diseases are difficult to understand, but because most of the scientists who contribute to them are molecular biologists and not doctors or system biology engineers.
*Detail from "Triumph of St. Thomas Aquinas over Averroes" by Benozzo Gozzoli (1420–97)*
Molecular biologists do not care for anatomy of physiology, even worse, they treat the 200 different types of cells in the body as mostly similar. Even if most of neurodegenerative diseases involve anatomical structures that are found only in primates, their animal models are non-primate, and indeed they are astonished that good clinical results in mice do not translate in human beings.
They do not even agree if ALS starts in the brain or in muscles ("dying forward" hypothesis versus "dying backward" hypothesis). Astonishingly several times they "proved" that each of their favorite hypothesis was true and that indeed the competing hypothesis was false.
For ALS alone they implicated more than 120 genes, even if the notion of gene (as a single DNA region which is uniquely implicated in coding a specific strand of RNA) is extremely vague. And they did this before finding that, what was thought as a non coding region (C9orf72) was implicated in ~50% of familial ALS cases. Now C9orf72 is called a gene, so everything is safe again.
Like medieval scholars who discussed how many angels could stand on the tip of a pin, they proposed thousands of small molecules as the causal mechanism for Alzheimer's, Parkinson's, or ALS. The profusion of proposals and the lack of discussion of competing proposals should surely question anyone with a rational mind?
And some authors have stated non-mainstream research proposals were blocked since decades.
This kind of scientist has lost credibility.
There are alternating views, notably by Heiko Braak who says that Parkinson and Alzheimer start with a pathogen invasion in guts and its subsequent progression into the brain. And he and his colleagues provided good evidence for that.
Braak is a medical doctor, but molecular biology scientists did not think much of his findings. Braak is cited only by 0.3% of articles on Parkinson disease.
For a better explanation of why trying to understand something by dissecting it in components and making experiments on isolated components does not help to comprehend how a system works, look at the famous article "Can a biologist fix a radio?"
So in my current view we call different neurodegenerative diseases with different names, but they are mostly the same disease. Whatever neurons are dying in the substantia nigra (Parkinson), primary motor cortex (ALS), or lobes (Alzheimer) it is mainly about neurons dying in the brain. And it is a problem that cannot be solved with molecular biology.