title: Hyperphosphorylated tau is elevated in Alzheimer's disease with psychosis.
abstract: Psychosis occurs in 40-60% of Alzheimer's disease (AD) subjects, is heritable, and indicates a more rapidly progressive disease phenotype. Neuroimaging and postmortem evidence support an exaggerated prefrontal cortical synaptic deficit in AD with psychosis. Microtubule-associated protein tau is a key mediator of amyloid-β-induced synaptotoxicity in AD, and differential mechanisms of progressive intraneuronal phospho-tau accumulation and interneuronal spread of tau aggregates have recently been described. We hypothesized that psychosis in AD would be associated with greater intraneuronal concentration of phospho-tau and greater spread of tau aggregates in prefrontal cortex. We therefore evaluated prefrontal cortex phospho-tau in a cohort of 45 AD cases with and without psychosis. Intraneuronal phospho-tau concentration was higher in subjects with psychosis, while a measure of phospho-tau spread, volume fraction, was not. Across groups both measures were associated with lower scores on the Mini-Mental State Examination and Digit Span Backwards test. These novel findings indicate that tau phosphorylation may be accelerated in AD with psychosis, indicating a more dynamic, exaggerated pathology in AD with psychosis.
authors.affiliation: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA VISN 4 Mental Illness Research, Education and Clinical Center, VA Pittsburgh Healthcare System, Pittsburgh, PA, USA.
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Murray
authors.affiliation: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Caitlin M
authors.initials: CM
authors.lastname: Kirkwood
authors.affiliation: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Megan C
authors.initials: MC
authors.lastname: Gray
authors.affiliation: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Kenneth N
authors.initials: KN
authors.lastname: Fish
authors.affiliation: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Geriatric Research Educational and Clinical Center, VA Pittsburgh Healthcare System, Pittsburgh, PA, USA.
authors.forename: Milos D
authors.initials: MD
authors.lastname: Ikonomovic
authors.affiliation: Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Hamilton
authors.affiliation: Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Julia K
authors.initials: JK
authors.lastname: Kofler
authors.affiliation: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: William E
authors.initials: WE
authors.lastname: Klunk
authors.affiliation: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Oscar L
authors.initials: OL
authors.lastname: Lopez
authors.affiliation: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA VISN 4 Mental Illness Research, Education and Clinical Center, VA Pittsburgh Healthcare System, Pittsburgh, PA, USA Department of Neurology, University of Pittsburgh School of Medicine, 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 / Q000378:metabolism* / Q000473:pathology* / Q000523:psychology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D010766:Phosphorylation / Q000502:physiology; D011618:Psychotic Disorders / Q000378:metabolism* / Q000473:pathology* / Q000523:psychology; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016875:tau Proteins
keywords: Alzheimer's disease; Braak stage; Mini-Mental State Examination; psychosis; tau