Defining novel functions for cerebrospinal fluid in ALS pathophysiology

TY - JOUR

T1 - Defining novel functions for cerebrospinal fluid in ALS pathophysiology

AU - Ng Kee Kwong, Koy Chong

AU - Mehta, Arpan R

AU - Nedergaard, Maiken

AU - Chandran, Siddharthan

N1 - © The Author(s). 2020

PY - 2020/8/20

Y1 - 2020/8/20

N2 - Despite the considerable progress made towards understanding ALS pathophysiology, several key features of ALS remain unexplained, from its aetiology to its epidemiological aspects. The glymphatic system, which has recently been recognised as a major clearance pathway for the brain, has received considerable attention in several neurological conditions, particularly Alzheimer's disease. Its significance in ALS has, however, been little addressed. This perspective article therefore aims to assess the possibility of CSF contribution in ALS by considering various lines of evidence, including the abnormal composition of ALS-CSF, its toxicity and the evidence for impaired CSF dynamics in ALS patients. We also describe a potential role for CSF circulation in determining disease spread as well as the importance of CSF dynamics in ALS neurotherapeutics. We propose that a CSF model could potentially offer additional avenues to explore currently unexplained features of ALS, ultimately leading to new treatment options for people with ALS.

AB - Despite the considerable progress made towards understanding ALS pathophysiology, several key features of ALS remain unexplained, from its aetiology to its epidemiological aspects. The glymphatic system, which has recently been recognised as a major clearance pathway for the brain, has received considerable attention in several neurological conditions, particularly Alzheimer's disease. Its significance in ALS has, however, been little addressed. This perspective article therefore aims to assess the possibility of CSF contribution in ALS by considering various lines of evidence, including the abnormal composition of ALS-CSF, its toxicity and the evidence for impaired CSF dynamics in ALS patients. We also describe a potential role for CSF circulation in determining disease spread as well as the importance of CSF dynamics in ALS neurotherapeutics. We propose that a CSF model could potentially offer additional avenues to explore currently unexplained features of ALS, ultimately leading to new treatment options for people with ALS.

KW - Glymphatic system

KW - Cerebrospinal fluid

KW - Amyotrophic lateral sclerosis

KW - Motor neuron disease

KW - Frontotemporal dementia

KW - Ageing

UR - https://www.scopus.com/pages/publications/85089769274

U2 - 10.1186/s40478-020-01018-0

DO - 10.1186/s40478-020-01018-0

M3 - Review article

C2 - 32819425

SN - 2051-5960

VL - 8

JO - Acta Neuropathologica Communications

JF - Acta Neuropathologica Communications

IS - 1

M1 - 140

ER -