title: Nucleolar PARP-1 Expression Is Decreased in Alzheimer's Disease: Consequences for Epigenetic Regulation of rDNA and Cognition.
abstract: Synaptic dysfunction is thought to play a major role in memory impairment in Alzheimer's disease (AD). PARP-1 has been identified as an epigenetic regulator of plasticity and memory. Thus, we hypothesize that PARP-1 may be altered in postmortem hippocampus of individuals with AD compared to age-matched controls without neurologic disease. We found a reduced level of PARP-1 nucleolar immunohistochemical staining in hippocampal pyramidal cells in AD. Nucleolar PARP-1 staining ranged from dispersed and less intense to entirely absent in AD compared to the distinct nucleolar localization in hippocampal pyramidal neurons in controls. In cases of AD, the percentage of hippocampal pyramidal cells with nucleoli that were positive for both PARP-1 and the nucleolar marker fibrillarin was significantly lower than in controls. PARP-1 nucleolar expression emerges as a sensitive marker of functional changes in AD and suggests a novel role for PARP-1 dysregulation in AD pathology.
authors.affiliation: Department of Pathology, State University of New York, Downstate Medical Center, Brooklyn, NY 11203, USA.
authors.forename: Jianying
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Department of Pathology, State University of New York, Downstate Medical Center, Brooklyn, NY 11203, USA; Department of Neurology, State University of New York, Downstate Medical Center, Brooklyn, NY 11203, USA.
authors.forename: Jenny
authors.initials: J
authors.lastname: Libien
authors.affiliation: Department of Pathology, State University of New York, Downstate Medical Center, Brooklyn, NY 11203, USA.
authors.forename: Fatima
authors.initials: F
authors.lastname: Shaik
authors.affiliation: Department of Physics, New York University, New York, NY 10003, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Wolk
authors.affiliation: Department of Pathology, State University of New York, Downstate Medical Center, Brooklyn, NY 11203, USA; The Robert F. Furchgott Center for Neural and Behavioral Science, State University of New York, Downstate Medical Center, Brooklyn, NY 11203, USA.
authors.forename: A Iván
authors.initials: AI
authors.lastname: Hernández
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D002466:Cell Nucleolus / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D003071:Cognition / Q000502:physiology*; D004275:DNA, Ribosomal / Q000378:metabolism; D044127:Epigenesis, Genetic; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D008297:Male; D000071137:Poly (ADP-Ribose) Polymerase-1 / Q000378:metabolism*; D017966:Pyramidal Cells / Q000378:metabolism
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004275:DNA, Ribosomal; C047458:fibrillarin; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1