The hypothesis (I'm paraphrasing) is the fructose severely downgrades the mitochondria (this is well established).
The part that is really interesting to me is that patients with alzheimer's have huge amounts of fructose in their brains (that's covered the in the podcast).
So, lots of fructose, mitochondria impacted, thus neurons degraded. Makes sense to me.
As far as alternative hypothesis, there aren't any good ones that I'm aware of.
Alzheimer's disease is a specific subtype of dementia; this article seems to be more focused on vascular dementia (or at least vascular risk factors) -- why I was curious about the relationship between e.g. smoking and fructose.
The association of fructose has been studied directly in the context of AD, and the hazard ratio is modest (and not necessarily dose-dependent) [0]:
> After adjustment for sex, age, MMSE at baseline, education level, SBP, treatment of hypertension, LDL, uric acid, prevalent diabetes mellitus, current smoking, alcohol consumption, dietary fiber intake, total energy intake, sugar in beverage, seafood, red meat, fried foods, animal fat, personal income, marital status, physical activity index, and BMI in the Cox regression model, participants with consumption of fructose more than 7 servings/week showed a higher risk of all-cause dementia and AD dementia (HR: 1.49, 95% CI: 1.14–1.84, P for trend < 0.001 for all-cause dementia; HR: 1.60, 95% CI: 1.22–2.01, P-trend < 0.001 for AD dementia) than subjects with no consumption for fructose. And the results remained comparable for participants with medium consumption of fructose (HR: 1.46, 95% CI: 1.30–1.79, for all-cause dementia; HR: 1.52, 95% CI: 1.14–1.91, for AD dementia) (see Table 2).
I haven't seen anything about the fructose content of brains of AD patients; do you have a (preferably non-video) reference / source?
[0]: https://www.sciencedirect.com/science/article/pii/S227458072...