Although known to be essential for all animals with nervous system, the main cellular function of sleep is still unknown. Prolonged sleep deprivation can be lethal, and sleep disturbances are associated with various deficiencies in brain performance. 

Far from being relaxed when we’re sleeping, our brains are very active and uses a lot of energy. Most of the energy is spent on important “housekeeping work” such as: cleaning up, consolidating memories, getting rid of data it doesn’t need and cleaning out physical waste products, including beta-Amyloid deposits.

The mechanisms underlying solute clearance from the brain’s extracellular space have puzzled neurologists for centuries, once the central nervous system (CNS) is the only organ system lacking lymphatic vessels to assist in the removal of interstitial metabolic waste products. Recent studies have led to the discovery of the glymphatic system, a glial-dependent perivascular network with a lymphatic-like function in the brain.

The glymphatic pathway is a highly-organized fluid transport system where cerebrospinal fluid (CSF) and interstitial fluid (ISF) continuously interchange. In its initial segments, CSF from the subarachnoid space flows into the brain through perivascular spaces of the large arteries and is driven into the brain parenchyma through the perivascular spaces of penetrating arteries, also known as Virchow-Robins spaces. This flow across the brain parenchyma is facilitated from the water channels aquaporin 4 (AQP4), a protein which is densely expressed by glial cells. While flowing, the CSF mixes with the ISF. In the interstitium, the mixed fluid disperses via a polarized net fluid movement directed towards the venous perivascular space (fig1).

Potential factors affecting glymphatic pathways include respiratory cycle, arterial pulsations, changes in vasomotor tone, postural changes and sleep. This last factor is significantly important in cleaning waste product: the clearance of amyloid beta (Aß) during sleep is twice as fast as during awake periods.

Besides cleaning, the brain also needs sleep to replenish itself. During REM-stage and dreaming the brain works on fixing any damage suffered during the daytime: restores the metabolic stores, trims unneeded synapses, reinforces specific connections and overall becomes more energy efficient. It also works repairing damaged DNA inside neurons, increases chromosome dynamics and performs nuclear maintenance. These changes in chromatin dynamics have been shown to regulate key nuclear processes, including epigenetic functions.


The glymphatic system is a recent described mechanism that our brain uses to eliminate physical waste products, like amyloid beta (Aß). This system works mainly during sleep, specially during deep stages of sleep. This may help to explain the biological need for sleep across all species and reinforces the importance of a good night of sleep.

Sleep well and allow yourself to experience a proper brain “detox”, helping to prevent AD.


    1. Tarasoff-Conway JM, Carare RO, Osorio RS, et al. Clearance systems in the brain-implications for Alzheimer disease [published correction appears in Nat Rev Neurol. 2016 Apr;12(4):248]. Nat Rev Neurol. 2015;11(8):457–470. doi:10.1038/nrneurol.2015.119
    2. Zada, D., Bronshtein, I., Lerer-Goldshtein, T. et al. Sleep increases chromosome dynamics to enable reduction of accumulating DNA damage in single neurons. Nat Commun 10, 895 (2019) doi:10.1038/s41467-019-08806-w
    3. Rasmussen MK, Mestre H, Nedergaard M. The glymphatic pathway in neurological disorders. Lancet Neurol. 2018;17(11):1016–1024. doi:10.1016/S1474-4422(18)30318-1
    4. Jessen NA, Munk AS, Lundgaard I, Nedergaard M. The Glymphatic System: A Beginner’s Guide. Neurochem Res. 2015;40(12):2583–2599. doi:10.1007/s11064-015-1581-6

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