title: Amyotrophic lateral sclerosis: Is the spinal fluid pathway involved in seeding and spread?
abstract: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder manifested primarily by loss of upper and lower motor neurons. Current explanations for disease progression invoke regional spread attributed to the transfer of pathogenic factors among physically contiguous neurons. However, this explanation incompletely explains certain clinical and in vitro data. Considering this, we propose that the cerebrospinal fluid (CSF) pathway is likely to be a key vector for seeding local and distal disease. Subsequent disease progression would be expected to occur independently via either axonal or CSF transmission. If one accepts the hypothesis that the CSF pathway is involved in ALS progression, it follows that the choroid plexus (CP) might well be a driver of the disease process. In support of this, we briefly review the anatomical and physiological features of the CSF pathway and the choroid plexus responsible for secreting CSF. In addition, we draw attention to the interface of the CP and CSF with the immune system. We then summarize both clinical and cell culture research that supports a key role of the CSF in the establishment and inter-neuronal spread of ALS, and which suggest directions for translational research.
authors.affiliation: Center for Neurologic Study, 7590 Fay Ave., Suite 517, La Jolla, CA 92037, United States. Electronic address: cnsonline@ymail.com.
authors.forename: Richard
authors.initials: R
authors.lastname: Smith
authors.affiliation: Center for Neurologic Study, 7590 Fay Ave., Suite 517, La Jolla, CA 92037, United States.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Myers
authors.affiliation: University of California San Diego School of Medicine, Dept. of Neurosciences, 9500 Gilman Dr. #0624, La Jolla, CA 92093, United States.
authors.forename: John
authors.initials: J
authors.lastname: Ravits
authors.affiliation: Barrow Neurological Institute, Gregory W. Fulton ALS and Neuromuscular Research Center, 350 West Thomas Rd., Phoenix, AZ 85013, United States.
authors.forename: Robert
authors.initials: R
authors.lastname: Bowser
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000503:physiopathology*; D002555:Cerebrospinal Fluid / Q000502:physiology*; D002831:Choroid Plexus / Q000503:physiopathology; D006801:Humans