title: Increased quinolinic acid in peripheral mononuclear cells in Alzheimer's dementia.
abstract: The role of monocytes and macrophages in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD) is poorly understood. Recently, we have shown that the number of CD14+ monocytes remained constant during healthy aging and in AD patients. Although only little is known about the function of activated macrophages and microglia in AD, one important mechanism involves the expression of quinolinic acid (QUIN), an endogenous N-methyl-D-aspartate glutamate receptor (NMDA-R) agonist which mediates excitotoxicity especially in the hippocampus. We used immunofluorescence stainings of PBMCs to determine the expression of quinolinic acid (QUIN) and the MHC class II molecule HLA-DR in peripheral monocytic cells in 51 healthy volunteers aged 22-87 years and 43 patients with AD at diagnosis (0 weeks) and during the course of rivastigmine treatment at 0.25 year (12 weeks), 0.5 year (30 weeks), 1 year, and 1.5 years. The number of QUIN+ HLA-DR+ cells rises in healthy persons aged 30-40 years compared to persons aged 60-70 years, indicating that this cell population increases with aging. AD patients at diagnosis had an increased frequency of QUIN+, QUIN+ HLA-DR+, and QUIN+ HLA-DR+/HLA-DR+ cells compared to aged-matched controls. These cell populations remained increased in AD for up to one year after initiation of treatment with rivastigmine; no alterations were detected in aged healthy persons. We conclude that the expression of the neurotoxic agent QUIN is increased in peripheral monocytes from AD patients. These cells could enter the brain and contribute to excitotoxicity.
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany. mandy.busse@gmx.de.
authors.forename: Mandy
authors.initials: M
authors.lastname: Busse
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Hettler
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany.
authors.forename: Victoria
authors.initials: V
authors.lastname: Fischer
authors.affiliation: Department of Neuropathology, University of Magdeburg, Magdeburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Mawrin
authors.affiliation: Institute of Immunology, University of Magdeburg, Magdeburg, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Hartig
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany.
authors.forename: Henrik
authors.initials: H
authors.lastname: Dobrowolny
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany.|Center for Behavioral Brain Sciences, Magdeburg, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Bogerts
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Frodl
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Busse
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D017378:Quinolinic Acid / Q000378:metabolism*; D055815:Young Adult
chemical_list: D017378:Quinolinic Acid
keywords: Alzheimer’s dementia; Monocytes; Quinolinic acid; Rivastigmine