The invention provides methods for diagnosing neurodegenerative disorders (e.g., amyotrophic lateral sclerosis and multiple sclerosis) in a subject, identifying subjects at risk of developing a neurodegenerative disorder, predicting the rate of disease progression in a subject having a neurodegenerative disorder, selecting a subject for treatment of a neurodegenerative disorder, selecting a subject for participation in a clinical study, and determining the efficacy of treatment of a neurodegenerative disorder. These methods include determining the level of one or more microRNAs and/or one or more inflammatory markers in a monocyte (e.g., a CD14+CD16- or CD14+CD16- monocyte) or in cerebrospinal fluid (CSF) from the subject and comparing the level of the one or more microRNAs and/or the level of the one or more inflammatory markers with a reference level(s). Also provided are methods of treating a neurodegenerative disorder that include administering to a subject at least one agent that decreases or increases the level or activity of one or more microRNAs or one or more inflammatory markers in a monocyte (e.g., a CD14+CD16- or CD14+CD16- monocyte) or in the CSF of a subject.
