While awaiting tau vaccine, I've considered a number of alternative ways in which to reduce existing phosphotau, in the absence of which it be possible to arrest Alzheimer's disease using current drugs or dietary interventions.
One obvious approach is some form of fasting. While it's well known that caloric restriction (CR) and intermittant fasting (IF) are beneficial to a wide variety of health parameters, they operate very differently in this regard. In particular, whereas CR seems to thwart amyloid and phosphotau deposition, IF appears to allow the brain to function better despite having little effect on such pathology. In other words, IF seems to seems to mimic the ketogenic diet as applied to established AD. But perhaps this is an erroneous conclusion based on differences in caloric consumption between the CR and IF groups in the former linked study: "Mice on the CR diet were provided an amount of food equal to 60% of that consumed by mice in the 3xTgAD [unrestricted control] group (40% caloric restriction). Mice on the IF diet were deprived of food for 24 h every other day." In other words, calorically equivalent CR and IF might be indistinguishable from the perspective of brain plaque; I have no informative data.
In a perfect world, we'd all be on CR in order to enjoy its many benefits on various health parameters, reduced brain plaque deposition being one of many. But CR is hard to follow, and leaves us more susceptible to musculoskeletal injury, excessive bleeding, and unexpected disruptions to eating ability (for example, infectious disease). On the plus side, we know that it upregulates autophagy, which in theory should clear intracellular junk like lipofuscin -- not merely thwart its formation in the first place. OTOH, does it also upregulate macroautophagy, that is, the clearance of extracellular junk by macrophages? Macroautophagy is absolutely necessary in order to clear cis-phosophotau, which is the gasoline that fuels the AD chain reaction.
If this works, then by implication, we don't need to worry much about maintaining CR. Instead, we can simply conduct a protracted water fast in order to maximize macroautophagy, wait for the plaque to clear, and then slowly refeed, perhaps under medical supervision. Obviously we can't clear 100% of the plaque, but what, in fact, would the upper limit be? If it were "enough to be useful", then we could simply fast, say, once a year, instead of partially fasting all the time (which is what CR amounts to, and why it's so frustrating to sustain).
Nevertheless, my default assumption is that macroautophagy isn't affected by CR at all. I mean, why should our microglia suddenly figure out how to clear phosphotau just because we're hungry? I don't think they would, because surviving CR in the wild is all about deeply engrained evolutionary pathways to cope with energy deficits -- not specific epitope targetting of junk proteins which exist outside the realm of cellular metobolism. What we need is a neon sign pinned to the debris piles, flagging them for collection, which in practical terms means that we need the monoclonal antibody in tau vaccine.
There is even some question regarding the use of CR to prevent AD in the first place: While CR might be superior to ketogenic diet for prevention of AD, the father of modern CR, Dr. Roy Walford, warned against its use in individuals suffering from neurodegenerative disease in some specific cases such as ALS. Unfortunately, I can't find his full explanation, which might well not apply to AD; tragically, he died of ALS himself.
So my question is: to what extent is what type of fasting capable of clearing existing extracellular phosphotau, as opposed to merely delaying its accumulation?
Edited by resveratrol_guy, 25 July 2015 - 03:24 PM.