Lulu Xie et al write in their paper Sleep Drives Metabolite Clearance from the Adult Brain:

Using real-time assessments of tetramethylammonium diffusion and two-photon imaging in live mice, we show that natural sleep or anesthesia are associated with a 60% increase in the interstitial space, resulting in a striking increase in convective exchange of cerebrospinal fluid with interstitial fluid. In turn, convective fluxes of interstitial fluid increased the rate of β-amyloid clearance during sleep.

Given that Alzheimer's patients have more β-amyloid in their brains, do they also have less interstitial space?


It's hard to judge whether interstitial space changes are due to beta amyloid accumulation or because the Alzheimer's brain has suffered such profound cell loss and neurodegeneration as a result.

The Nedergaard paper you quote is more about a daily cycle of increase/decrease in interstitial space related to the sleep/wake cycle [Ref 1]. Specifically, that during sleep, there is more space to flush out the brain including beta-amyloid. One interesting hypothesis from that being that perhaps the accumulation of these aggregates is actually due to inefficient sleep -> inefficient flushing of plaques which go on to give symptoms. So even if the interstitial space in what's left of the Alzheimer's brain remained the same as a healthy brain, the problem of beta amyloid clearance could still be present. It remains to be seen if one could restore normal clearance whether degeneration could be slowed and symptoms abated.

[Ref. 1]: Paper from Nedergaard group


Your Answer

By clicking “Post Your Answer”, you agree to our terms of service, privacy policy and cookie policy

Not the answer you're looking for? Browse other questions tagged or ask your own question.