title: Profiles of extracellular miRNA in cerebrospinal fluid and serum from patients with Alzheimer's and Parkinson's diseases correlate with disease status and features of pathology.
abstract: The discovery and reliable detection of markers for neurodegenerative diseases have been complicated by the inaccessibility of the diseased tissue--such as the inability to biopsy or test tissue from the central nervous system directly. RNAs originating from hard to access tissues, such as neurons within the brain and spinal cord, have the potential to get to the periphery where they can be detected non-invasively. The formation and extracellular release of microvesicles and RNA binding proteins have been found to carry RNA from cells of the central nervous system to the periphery and protect the RNA from degradation. Extracellular miRNAs detectable in peripheral circulation can provide information about cellular changes associated with human health and disease. In order to associate miRNA signals present in cell-free peripheral biofluids with neurodegenerative disease status of patients with Alzheimer's and Parkinson's diseases, we assessed the miRNA content in cerebrospinal fluid and serum from postmortem subjects with full neuropathology evaluations. We profiled the miRNA content from 69 patients with Alzheimer's disease, 67 with Parkinson's disease and 78 neurologically normal controls using next generation small RNA sequencing (NGS). We report the average abundance of each detected miRNA in cerebrospinal fluid and in serum and describe 13 novel miRNAs that were identified. We correlated changes in miRNA expression with aspects of disease severity such as Braak stage, dementia status, plaque and tangle densities, and the presence and severity of Lewy body pathology. Many of the differentially expressed miRNAs detected in peripheral cell-free cerebrospinal fluid and serum were previously reported in the literature to be deregulated in brain tissue from patients with neurodegenerative disease. These data indicate that extracellular miRNAs detectable in the cerebrospinal fluid and serum are reflective of cell-based changes in pathology and can be used to assess disease progression and therapeutic efficacy.
authors.affiliation: Neurogenomics, Translational Genomics Research Institute (TGen), Phoenix, Arizona, United States of America.
authors.forename: Kasandra
authors.initials: K
authors.lastname: Burgos
authors.affiliation: Neurogenomics, Translational Genomics Research Institute (TGen), Phoenix, Arizona, United States of America.
authors.forename: Ivana
authors.initials: I
authors.lastname: Malenica
authors.affiliation: Neurogenomics, Translational Genomics Research Institute (TGen), Phoenix, Arizona, United States of America.
authors.forename: Raghu
authors.initials: R
authors.lastname: Metpally
authors.affiliation: Neurogenomics, Translational Genomics Research Institute (TGen), Phoenix, Arizona, United States of America.
authors.forename: Amanda
authors.initials: A
authors.lastname: Courtright
authors.affiliation: Neurogenomics, Translational Genomics Research Institute (TGen), Phoenix, Arizona, United States of America.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Rakela
authors.affiliation: Neurology, Banner Sun Health Research Institute, Sun City, Arizona, United States of America.
authors.forename: Thomas
authors.initials: T
authors.lastname: Beach
authors.affiliation: Neurology, Banner Sun Health Research Institute, Sun City, Arizona, United States of America.
authors.forename: Holly
authors.initials: H
authors.lastname: Shill
authors.affiliation: Neurology, Mayo Clinic, Scottsdale, Arizona, United States of America.
authors.forename: Charles
authors.initials: C
authors.lastname: Adler
authors.affiliation: Neurology, Banner Sun Health Research Institute, Sun City, Arizona, United States of America.
authors.forename: Marwan
authors.initials: M
authors.lastname: Sabbagh
authors.affiliation: Neurogenomics, Translational Genomics Research Institute (TGen), Phoenix, Arizona, United States of America.
authors.forename: Stephen
authors.initials: S
authors.lastname: Villa
authors.affiliation: Neurogenomics, Translational Genomics Research Institute (TGen), Phoenix, Arizona, United States of America.
authors.forename: Waibhav
authors.initials: W
authors.lastname: Tembe
authors.affiliation: Neurogenomics, Translational Genomics Research Institute (TGen), Phoenix, Arizona, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Craig
authors.affiliation: Neurogenomics, Translational Genomics Research Institute (TGen), Phoenix, Arizona, United States of America.
authors.forename: Kendall
authors.initials: K
authors.lastname: Van Keuren-Jensen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000134:cerebrospinal fluid / Q000473:pathology / Q000628:therapy; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000134:cerebrospinal fluid*; D010300:Parkinson Disease / Q000097:blood / Q000134:cerebrospinal fluid / Q000473:pathology / Q000628:therapy
chemical_list: D035683:MicroRNAs