title: Psychotic Alzheimer's disease is associated with gender-specific tau phosphorylation abnormalities.
abstract: Converging evidence suggests that psychotic Alzheimer's disease (AD + P) is associated with an acceleration of frontal degeneration, with tau pathology playing a primary role. Previous histopathologic and biomarker studies have specifically implicated tau pathology in this condition. To precisely quantify tau abnormalities in the frontal cortex in AD + P, we used a sensitive biochemical assay of total tau and 4 epitopes of phospho-tau relevant in AD pathology in a postmortem sample of AD + P and AD - P. Samples of superior frontal gyrus from 26 AD subjects without psychosis and 45 AD + P subjects with psychosis were analyzed. Results of enzyme-linked immunosorbent assay demonstrate that AD + P females, but not males, had significantly higher levels of phosphorylated tau in the frontal cortex. In males, but not females, AD + P was associated with the presence of α-synuclein pathology. These results support a gender dissociation of pathology in AD + P. The design of future studies aimed at the elucidation of cognitive and/or functional outcomes; regional brain metabolic deficits; or genetic correlates of AD + P should take gender into consideration.
authors.affiliation: The Litwin-Zucker Research Center for the Study of Alzheimer's Disease, The Feinstein Institute for Medical Research, Manhasset, NY, USA; The Zucker Hillside Hospital, The North-Shore LIJ Health System, Glen Oaks, NY, USA. Electronic address: jkoppel@nshs.edu.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Koppel
authors.affiliation: The Litwin-Zucker Research Center for the Study of Alzheimer's Disease, The Feinstein Institute for Medical Research, Manhasset, NY, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Acker
authors.affiliation: The Litwin-Zucker Research Center for the Study of Alzheimer's Disease, The Feinstein Institute for Medical Research, Manhasset, NY, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Davies
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA; Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Oscar L
authors.initials: OL
authors.lastname: Lopez
authors.affiliation: The Litwin-Zucker Research Center for the Study of Alzheimer's Disease, The Feinstein Institute for Medical Research, Manhasset, NY, USA.
authors.forename: Heidy
authors.initials: H
authors.lastname: Jimenez
authors.affiliation: Touro College, Brooklyn, NY, USA.
authors.forename: Miriam
authors.initials: M
authors.lastname: Azose
authors.affiliation: The Zucker Hillside Hospital, The North-Shore LIJ Health System, Glen Oaks, NY, USA.
authors.forename: Blaine S
authors.initials: BS
authors.lastname: Greenwald
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA; Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Murray
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA; Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Caitlin M
authors.initials: CM
authors.lastname: Kirkwood
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA; Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Julia
authors.initials: J
authors.lastname: Kofler
authors.affiliation: The Litwin-Zucker Research Center for the Study of Alzheimer's Disease, The Feinstein Institute for Medical Research, Manhasset, NY, USA; Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA; Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA; VISN Q2 4 Mental Illness Research, Education and Clinical Center (MIRECC), VA Pittsburgh Healthcare System, Pittsburgh, PA, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Sweet
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000378:metabolism* / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008297:Male; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D011618:Psychotic Disorders / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D012727:Sex Characteristics; D051844:alpha-Synuclein / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D051844:alpha-Synuclein; D016875:tau Proteins
keywords: Alpha-synuclein; Alzheimer's disease; Dementia with Lewy bodies; Neurofibrillary tangles; Psychosis; Tau
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