Although the “Abeta protein aggregates cause Alzheimer’s disease” has had quite a run, it is not our most common assumption about Alzheimer’s disease.
Any guesses?
The assumption is hidden in the deep in the semantics of Alzheimer’s disease. By simply naming it we are tacitly assuming that Alzheimer’s disease is just one thing. The history of medicine is the history of splitting diagnostic categories with the passage of time due the accumulation of causal knowledge.
Infections were characterized by the type of fever they produced before Pasteur. Breast cancer was characterized by pathology before it was molecularly split depending which hormone receptors were present. No one would dream of treating it all the same way today.
Yet here we have massive clinical trials of single therapies in Alzheimer’s disease because we don’t know any better.
Because people vary, in all clinical trials the responses to a given drug vary patient to patient. It is worth studying those responding best and those responding worst to a therapy in terms of the data taken on entry (MMSE, age, sex, education, pre-existing disease, smoking drinking, etc. etc.). Such analysis might tell us something about the underlying causes in addition to predicting who will and who won’t respond in the future.
In particular, Cassava Sciences’ recent release of two years of open label Simufilam administration should be studied this way. The second year is problematic as some dropped out, some continued to receive the Simufilam, some did not, but all patients still in the study at one year had been on the drug for a year, and their clinical data (ADAS-Cog etc. etc.) is in Cassava’s possession.
How did the group responding best differ from those responding the least. Lindsay is too busy dealing with the slings and arrows of outrageous fortune (courtesy of Science, the Wall Street Journal etc. etc.) to climb an academic totem pole to write it up.
I am particularly interested in the 5/50 patients Lindsay reported 8/21 who likely showed a 50% improvement at 9 months. As a clinical neurologist with decades of experience with demented patients, I never saw this degree of improvement at 9 months. How did the 5 do at one year and, if continuing on Simufilam, how did they do at two years? What was different about the 5 as a group vs. the 45 that didn’t do as well?
To have a look at the actual data Lindsay presented back then follow this link — https://luysii.wordpress.com/2021/08/25/cassava-sciences-9-month-data-is-probably-better-than-they-realize/
Chemiotics II 
Comments
Can they identify a population of patients where the benefits of treatment outweigh the risks. Our patients deserve better treatment options
So, instead of thinking “Alzheimer’s is a form of dementia” we may need to be thinking “Alzheimer’s is a class of dementia”. In my head, that seems like the shift between “so-and-so is depressed” and “so-and-so has seasonal/atypical/dysthymic/post-trauma depression”.
It may help to do ancestor tracing, too. (The DNA kind, as it’s faster than perusing old records.) For location influences (terrain influence), latitude influences (season change timing), and ancestral influences (English vs Irish vs Spaniard). The epigenentic evidence shown regarding the Great Depression’s effect on 3 generations of women points to extra effects in the background.
Using myself as a slight example (and a few anthropology papers I’ve read), I’ve got the tougher skin of neanderthal hybrids. (Like leather in baseball mitts, per doctors stitching me up.) That strong expression likely has background effects that color how I would respond.