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Title:
Novel CSF biomarkers for Alzheimer’s disease and mild cognitive impairment | Acta Neuropathologica
Description:
Altered levels of cerebrospinal fluid (CSF) peptides related to Alzheimer’s disease (AD) are associated with pathologic AD diagnosis, although cognitively normal subjects can also have abnormal levels of these AD biomarkers. To identify novel CSF biomarkers that distinguish pathologically confirmed AD from cognitively normal subjects and patients with other neurodegenerative disorders, we collected antemortem CSF samples from 66 AD patients and 25 patients with other neurodegenerative dementias followed longitudinally to neuropathologic confirmation, plus CSF from 33 cognitively normal subjects. We measured levels of 151 novel analytes via a targeted multiplex panel enriched in cytokines, chemokines and growth factors, as well as established AD CSF biomarkers (levels of Aβ42, tau and p-tau181). Two categories of biomarkers were identified: (1) analytes that specifically distinguished AD (especially CSF Aβ42 levels) from cognitively normal subjects and other disorders; and (2) analytes altered in multiple diseases (NrCAM, PDGF, C3, IL-1α), but not in cognitively normal subjects. A multi-prong analytical approach showed AD patients were best distinguished from non-AD cases (including cognitively normal subjects and patients with other neurodegenerative disorders) by a combination of traditional AD biomarkers and novel multiplex biomarkers. Six novel biomarkers (C3, CgA, IL-1α, I-309, NrCAM and VEGF) were correlated with the severity of cognitive impairment at CSF collection, and altered levels of IL-1α and TECK associated with subsequent cognitive decline in 38 longitudinally followed subjects with mild cognitive impairment. In summary, our targeted proteomic screen revealed novel CSF biomarkers that can improve the distinction between AD and non-AD cases by established biomarkers alone.
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article, pubmed, google, scholar, cas, biomarkers, alzheimers, disease, cerebrospinal, fluid, csf, subjects, usa, neurol, lee, medicine, research, cognitive, levels, diagnosis, normal, university, school, trojanowski, cognitively, access, neurology, pennsylvania, philadelphia, privacy, cookies, content, acta, mild, impairment, clark, john, patients, neurodegenerative, department, publish, search, march, william, chenplotkin, grossman, shaw, virginia, related, growth,
Topics {✒️}
beta-gamma-secretase-mediated cleavage lymphocyte-attracting chemokines teck/mccl25 month download article/chapter platelet-derived growth factor ankyrin-binding protein nrcam neurofascin/l1/nrcam family src-rac-dependent pathway neuronal degeneration markers cerebrospinal fluid tau pfizer global research amyloid precursor protein yu chen & holly soares cerebrospinal fluid profile full article pdf tau proteins beta-amyloid beta-cell function plasma signaling proteins privacy choices/manage cookies mild cognitive impairment mild cognitive impairment il-1α subsequent cognitive decline penn-pfizer alliance cognitively normal subjects neuronal cell bodies pathologic ad diagnosis demented elderly subjects neurodegenerative disease research frontotemporal dementia international working group check access instant access european economic area detergent-insoluble subproteome pdd boundary issues leukocyte migration control amyotrophic lateral sclerosis potential diagnostic marker mouse ccx-ckr mip-3beta/mccl19 human ccx-ckr ionizing radiation response nih k08 ag033101 maloney 3rd floor clark cm cerebrospinal fluid clinical diagnostic criteria conditions privacy policy neuropathologically-confirmed alzheimer
Questions {❓}
- Clark CM, Xie S, Chittams J et al (2003) Cerebrospinal fluid tau and beta-amyloid: how well do these biomarkers reflect autopsy-confirmed dementia diagnoses?
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headline:Novel CSF biomarkers for Alzheimer’s disease and mild cognitive impairment
description:Altered levels of cerebrospinal fluid (CSF) peptides related to Alzheimer’s disease (AD) are associated with pathologic AD diagnosis, although cognitively normal subjects can also have abnormal levels of these AD biomarkers. To identify novel CSF biomarkers that distinguish pathologically confirmed AD from cognitively normal subjects and patients with other neurodegenerative disorders, we collected antemortem CSF samples from 66 AD patients and 25 patients with other neurodegenerative dementias followed longitudinally to neuropathologic confirmation, plus CSF from 33 cognitively normal subjects. We measured levels of 151 novel analytes via a targeted multiplex panel enriched in cytokines, chemokines and growth factors, as well as established AD CSF biomarkers (levels of Aβ42, tau and p-tau181). Two categories of biomarkers were identified: (1) analytes that specifically distinguished AD (especially CSF Aβ42 levels) from cognitively normal subjects and other disorders; and (2) analytes altered in multiple diseases (NrCAM, PDGF, C3, IL-1α), but not in cognitively normal subjects. A multi-prong analytical approach showed AD patients were best distinguished from non-AD cases (including cognitively normal subjects and patients with other neurodegenerative disorders) by a combination of traditional AD biomarkers and novel multiplex biomarkers. Six novel biomarkers (C3, CgA, IL-1α, I-309, NrCAM and VEGF) were correlated with the severity of cognitive impairment at CSF collection, and altered levels of IL-1α and TECK associated with subsequent cognitive decline in 38 longitudinally followed subjects with mild cognitive impairment. In summary, our targeted proteomic screen revealed novel CSF biomarkers that can improve the distinction between AD and non-AD cases by established biomarkers alone.
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Amyloid beta
Abeta42
Diagnosis
IL-1α
MCI
NrCAM
PDGF
Resistin
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TDP-43
Tau
Pathology
Neurosciences
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headline:Novel CSF biomarkers for Alzheimer’s disease and mild cognitive impairment
description:Altered levels of cerebrospinal fluid (CSF) peptides related to Alzheimer’s disease (AD) are associated with pathologic AD diagnosis, although cognitively normal subjects can also have abnormal levels of these AD biomarkers. To identify novel CSF biomarkers that distinguish pathologically confirmed AD from cognitively normal subjects and patients with other neurodegenerative disorders, we collected antemortem CSF samples from 66 AD patients and 25 patients with other neurodegenerative dementias followed longitudinally to neuropathologic confirmation, plus CSF from 33 cognitively normal subjects. We measured levels of 151 novel analytes via a targeted multiplex panel enriched in cytokines, chemokines and growth factors, as well as established AD CSF biomarkers (levels of Aβ42, tau and p-tau181). Two categories of biomarkers were identified: (1) analytes that specifically distinguished AD (especially CSF Aβ42 levels) from cognitively normal subjects and other disorders; and (2) analytes altered in multiple diseases (NrCAM, PDGF, C3, IL-1α), but not in cognitively normal subjects. A multi-prong analytical approach showed AD patients were best distinguished from non-AD cases (including cognitively normal subjects and patients with other neurodegenerative disorders) by a combination of traditional AD biomarkers and novel multiplex biomarkers. Six novel biomarkers (C3, CgA, IL-1α, I-309, NrCAM and VEGF) were correlated with the severity of cognitive impairment at CSF collection, and altered levels of IL-1α and TECK associated with subsequent cognitive decline in 38 longitudinally followed subjects with mild cognitive impairment. In summary, our targeted proteomic screen revealed novel CSF biomarkers that can improve the distinction between AD and non-AD cases by established biomarkers alone.
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name:Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, USA
type:PostalAddress
type:Organization
name:University of Pennsylvania School of Medicine
address:
name:Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, USA
type:PostalAddress
type:Organization
name:University of Pennsylvania School of Medicine
address:
name:Institute on Aging, University of Pennsylvania School of Medicine, Philadelphia, USA
type:PostalAddress
type:Organization
email:[email protected]
PostalAddress:
name:Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, USA
name:Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, USA
name:Department of Neurology, Emory University School of Medicine, Atlanta, USA
name:Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, USA
name:Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, USA
name:Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, USA
name:Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, USA
name:Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, USA
name:Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, USA
name:Pfizer Global Research and Development, Groton, USA
name:Pfizer Global Research and Development, Groton, USA
name:Pfizer Global Research and Development, Groton, USA
name:Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, USA
name:Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, USA
name:Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, USA
name:Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, USA
name:Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, USA
name:Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, USA
name:Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, USA
name:Institute on Aging, University of Pennsylvania School of Medicine, Philadelphia, USA
name:Pfizer Global Research and Development, Groton, USA
name:Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, USA
name:Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, USA
name:Institute on Aging, University of Pennsylvania School of Medicine, Philadelphia, USA
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