TY - JOUR

T1 - The glymphatic system and Amyotrophic lateral sclerosis

AU - Eisen, Andrew

AU - Nedergaard, Maiken

AU - Gray, Emma

AU - Kiernan, Matthew C.

N1 - Publisher Copyright: © 2024 Elsevier Ltd

PY - 2024

Y1 - 2024

N2 - The glymphatic system and the meningeal lymphatic vessels provide a pathway for transport of solutes and clearance of toxic material from the brain. Of specific relevance to ALS, this is applicable for TDP-43 and glutamate, both major elements in disease pathogenesis. Flow is propelled by arterial pulsation, respiration, posture, as well as the positioning and proportion of aquaporin-4 channels (AQP4). Non-REM slow wave sleep is the is key to glymphatic drainage which discontinues during wakefulness. In Parkinson's disease and Alzheimer's disease, sleep impairment is known to predate the development of characteristic clinical features by several years and is associated with progressive accumulation of toxic proteinaceous products. While sleep issues are well described in ALS, consideration of preclinical sleep impairment or the potential of a failing glymphatic system in ALS has rarely been considered. Here we review how the glymphatic system may impact ALS. Preclinical sleep impairment as an unrecognized major risk factor for ALS is considered, while potential therapeutic options to improve glymphatic flow are explored.

AB - The glymphatic system and the meningeal lymphatic vessels provide a pathway for transport of solutes and clearance of toxic material from the brain. Of specific relevance to ALS, this is applicable for TDP-43 and glutamate, both major elements in disease pathogenesis. Flow is propelled by arterial pulsation, respiration, posture, as well as the positioning and proportion of aquaporin-4 channels (AQP4). Non-REM slow wave sleep is the is key to glymphatic drainage which discontinues during wakefulness. In Parkinson's disease and Alzheimer's disease, sleep impairment is known to predate the development of characteristic clinical features by several years and is associated with progressive accumulation of toxic proteinaceous products. While sleep issues are well described in ALS, consideration of preclinical sleep impairment or the potential of a failing glymphatic system in ALS has rarely been considered. Here we review how the glymphatic system may impact ALS. Preclinical sleep impairment as an unrecognized major risk factor for ALS is considered, while potential therapeutic options to improve glymphatic flow are explored.

KW - Amyotrophic lateral sclerosis

KW - Epidemiology

KW - Glymphatic system

KW - Neurodegeneration

KW - Sleep

U2 - 10.1016/j.pneurobio.2024.102571

DO - 10.1016/j.pneurobio.2024.102571

M3 - Review

C2 - 38266701

AN - SCOPUS:85183475322

VL - 234

JO - Progress in Neurobiology

JF - Progress in Neurobiology

SN - 0301-0082

M1 - 102571

ER -