Plasma and cerebrospinal fluid α1-antichymotrypsin levels in Alzheimer's disease: Correlation with cognitive impairment

Authors

  • Steven T. DeKosky MD,

    Corresponding author
    1. Department of Neurology and the Alzheimer's Disease Research Center, University of Pittsburgh, Pittsburgh, PA
    2. Department of Psychiatry and the Alzheimer's Disease Research Center, University of Pittsburgh, Pittsburgh, PA
    3. Department of Human Genetics Graduate School of Public Health, University of Pittsburgh Medical Center, Pittsburgh, PA
    • Alzheimer's Disease Research Center, University of Pittsburgh Medical Center, MUH 4th Floor, 200 Lothrop Street, Pittsburgh, PA 15213
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  • Milos D. Ikonomovic MD,

    1. Department of Psychiatry and the Alzheimer's Disease Research Center, University of Pittsburgh, Pittsburgh, PA
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  • Xiaoyan Wang PhD,

    1. Department of Human Genetics Graduate School of Public Health, University of Pittsburgh Medical Center, Pittsburgh, PA
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  • Martin Farlow MD,

    1. Department of Neurology, Indiana University School of Medicine, Indianapolis, IN
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  • Stephen Wisniewski PhD,

    1. Department of Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, PA
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  • Oscar L. Lopez MD,

    1. Department of Neurology and the Alzheimer's Disease Research Center, University of Pittsburgh, Pittsburgh, PA
    2. Department of Human Genetics Graduate School of Public Health, University of Pittsburgh Medical Center, Pittsburgh, PA
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  • James T. Becker PhD,

    1. Department of Psychiatry and the Alzheimer's Disease Research Center, University of Pittsburgh, Pittsburgh, PA
    2. Department of Human Genetics Graduate School of Public Health, University of Pittsburgh Medical Center, Pittsburgh, PA
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  • Judith Saxton PhD,

    1. Department of Psychiatry and the Alzheimer's Disease Research Center, University of Pittsburgh, Pittsburgh, PA
    2. Department of Human Genetics Graduate School of Public Health, University of Pittsburgh Medical Center, Pittsburgh, PA
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  • William E. Klunk MD, PhD,

    1. Department of Psychiatry and the Alzheimer's Disease Research Center, University of Pittsburgh, Pittsburgh, PA
    2. Department of Human Genetics Graduate School of Public Health, University of Pittsburgh Medical Center, Pittsburgh, PA
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  • Robert Sweet MD,

    1. Department of Psychiatry and the Alzheimer's Disease Research Center, University of Pittsburgh, Pittsburgh, PA
    2. Department of Human Genetics Graduate School of Public Health, University of Pittsburgh Medical Center, Pittsburgh, PA
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  • Daniel I. Kaufer MD,

    1. Department of Neurology and the Alzheimer's Disease Research Center, University of Pittsburgh, Pittsburgh, PA
    2. Department of Human Genetics Graduate School of Public Health, University of Pittsburgh Medical Center, Pittsburgh, PA
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  • M. Ilyas Kamboh PhD

    1. Department of Psychiatry and the Alzheimer's Disease Research Center, University of Pittsburgh, Pittsburgh, PA
    2. Department of Human Genetics Graduate School of Public Health, University of Pittsburgh Medical Center, Pittsburgh, PA
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Abstract

α-1-Antichymotrypsin (ACT) is present in neuritic plaques in which it participates in the inflammatory cascade of Alzheimer's disease (AD). Reports of blood ACT levels in AD, and its usefulness as a disease biomarker, have been conflicting. In an effort to clarify this, we measured plasma ACT levels in 516 white subjects including 359 subjects with probable or possible AD, 44 subjects with other late-life dementias, and 113 nondemented people. Subjects with systemic inflammatory diseases or who were taking antiinflammatory medications were excluded. All patients underwent extensive medical and detailed neuropsychological examinations at the time their blood was drawn. We found that plasma ACT levels were elevated in AD patients compared with the control group (p = 0.01) and were associated with severity of AD dementia; there was a negative association with the Mattis Dementia Rating Scale (a global measure of cognition) and a positive association with the Clinical Dementia Rating Scale (a global functional assessment). These relationships remained significant after controlling for demographic and genetic variables. When AD subjects were stratified into subgroups by dementia severity, matched by age, education, and gender, increased serum ACT correlated with Clinical Dementia Rating Scale (p = 0.0041) or Mattis Dementia Rating Scale (p = 0.0031) scores. ACT measurements in cerebrospinal fluid from an additional 34 AD cases and 16 controls showed elevated levels (p = 0.02) in AD. There was a negative correlation (p = 0.037) between cerebrospinal fluid ACT levels and clinical severity as measured by the Mini-Mental State Examination. Our results demonstrate that peripheral ACT levels are elevated in AD, but not in dementias other than AD, and they increase with progression of AD dementia. Although not useful as a diagnostic biomarker, ACT may reflect disease severity and may be helpful as a within subject biomarker in interventions (particularly with antiinflammatory agents) directed at slowing or halting progression of disease.

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