title: Aggregates of small nuclear ribonucleic acids (snRNAs) in Alzheimer's disease.
abstract: We recently discovered that protein components of the ribonucleic acid (RNA) spliceosome form cytoplasmic aggregates in Alzheimer's disease (AD) brain, resulting in widespread changes in RNA splicing. However, the involvement of small nuclear RNAs (snRNAs), also key components of the spliceosome complex, in the pathology of AD remains unknown. Using immunohistochemical staining of post-mortem human brain and spinal cord, we identified cytoplasmic tangle-shaped aggregates of snRNA in both sporadic and familial AD cases but not in aged controls or other neurodegenerative disorders. Immunofluorescence using antibodies reactive with the 2,2,7-trimethylguanosine cap of snRNAs and transmission electron microscopy demonstrated snRNA localization with tau and paired helical filaments, the main component of neurofibrillary tangles. Quantitative real-time polymerase chain reaction (PCR) showed U1 snRNA accumulation in the insoluble fraction of AD brains whereas other U snRNAs were not enriched. In combination with our previous results, these findings demonstrate that aggregates of U1 snRNA and U1 small nuclear ribonucleoproteins represent a new pathological hallmark of AD.
authors.affiliation: Center for Neurodegenerative Disease, Emory University, Atlanta, GA; Department of Neurology, Emory University School of Medicine, Atlanta, GA.
authors.forename: Chadwick M
authors.initials: CM
authors.lastname: Hales
authors.forename: Eric B
authors.initials: EB
authors.lastname: Dammer
authors.forename: Ian
authors.initials: I
authors.lastname: Diner
authors.forename: Hong
authors.initials: H
authors.lastname: Yi
authors.forename: Nicholas T
authors.initials: NT
authors.lastname: Seyfried
authors.forename: Marla
authors.initials: M
authors.lastname: Gearing
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Glass
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Montine
authors.forename: Allan I
authors.initials: AI
authors.lastname: Levey
authors.forename: James J
authors.initials: JJ
authors.lastname: Lah
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D008297:Male; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000378:metabolism; D012342:RNA, Small Nuclear / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D013116:Spinal Cord / Q000378:metabolism*; D024801:Tauopathies / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
chemical_list: C054369:MAPT protein, human; D012342:RNA, Small Nuclear; D016875:tau Proteins
keywords: 2,2,7-trimethylguanosine; ALS; Alzheimer's disease; RNA spliceosome; quantitative PCR; snRNA