Lack of sleep boosts levels of Alzheimer's proteins

It sounds like there is also genetic variation in production, so if you have a generally lower production then a higher level due to your sleep pattern might still not be that high relative to others (or if you have higher than usual production then long days could be more likely to cause trouble).

As someone with a circadian disorder, the thing I would worry about most from your sleep pattern is triggering a circadian disorder. At least Non-24 seems likely to have both a genetic predisposition and require triggering in many people (some have it from birth). This would be most likely if your normal rhythm seems to normally be longer than usual, although even there it isn't necessarily a problem since cave studes show people slip naturally into the type of sleep pattern that you describe. It might depend on how you do the transition (and how close you get to a two day cycle on your long days). But I would suggest at least being very observant of your circadian rhythm. Things like when you get hungry, feel tired, and have to pee can indicate how your circadian rhythm is doing and if those things change when you aren't staying up late then that could cause serious trouble eventually.

Prolonging the clearing process would mean that you spend a longer time at very low concentration, but not that the minimum concentration would be much lower. If the harm of high concentrations is disproportionally higher, the longer time at lower concentration would be unable to balance that out.

However, this is only based on my rough intuition and I didn't even do any napkin math. If you want to really get a quantifiable comparison, you'd better find out about the concrete interactions in question and calculate it yourself.

Or you could ask a physician who specializes in sleep (I forget what they are called), but if it isn't already published science somewhere, it's unlikely they could tell you anything other than that what you're doing is highly unusual and you should probably stop.

But I started logging my sleep times after an appointment with a sleep disorder clinic and found maybe I am not sleeping for as long as I assumed - it's just that when my sleep is interrupted, I don't complete my 8 hours until 12 or so has passed.

They mention one alternative that would also fit the data: "In order for decreased glymphatic clearance during sleep deprivation to increase soluble CSF Aβ, a decrease in irreversible losses (e.g. to the bloodstream or lymphatics) due to prolonged overnight waking would have to be perfectly matched by an increase in Aβ clearance to CSF. This is plausible but unlikely and not identifiable from the current data."

They say "The SILK kinetics results unequivocally show that glymphatic clearance alone, without compensation from other clearance mechanisms, would be ineffective in protecting the brain from AD because overall clearance rates are not changing. Glymphatic clearance may potentially contribute to the protective effects of sleep against AD, but changes in production rate seem to be the necessary and critical factor."

Also worth noting that they were unable to test if changes in slow wave sleep made a difference because sodium oxybate didn't actually increase slow wave sleep in that group vs normal sleepers.

It does sound like this contradicts previous research, at least: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3880190/

They do cite that paper but do not have a detailed analysis of how their results could be consistant or are contradictory to what that study found. In that study radioactive amyloid beta was directly injected into mice and then how much of it was left was observed after varying amounts of time later and in sleeping vs. awake vs anesthetized. Maybe newly produced amyloid beta could be cleared instead of the radiolabeled amyloid beta or maybe the injected amyloid beta had different clearanace properties than naturally generated amyloid beta, but I don't know if either of those are plausable. Maybe they are just contradictory results.

If it is correct that the production changes are what makes the difference, I wonder why that is the case considering the much larger fluid exchange that happens at night. Also I wonder if some of the other similar substances that cause problems if they accumulate too much have a similar issue. Maybe stuff that can be cleared at high rate is easier to get rid of with relatively little sleep and stuff that can't is more likely to cause trouble over time.