Altered Levels of Visinin-Like Protein 1 Correspond to Regional Neuronal Loss in Alzheimer Disease and Frontotemporal Lobar Degeneration

Recent studies have implicated the neuronal calcium-sensing protein visinin-like 1 protein (Vilip-1) as a peripheral biomarker in Alzheimer disease (AD), but little is known about expression of Vilip-1 in the brains of patients with AD. We used targeted and quantitative mass spectrometry to measure...

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Published inJournal of neuropathology and experimental neurology Vol. 75; no. 2; pp. 175 - 182
Main Authors Kirkwood, Caitlin M., MacDonald, Matthew L., Schempf, Tadhg A., Vatsavayi, Anil V., Ikonomovic, Milos D., Koppel, Jeremy L., Ding, Ying, Sun, Mai, Kofler, Julia K., Lopez, Oscar L., Yates, Nathan A., Sweet, Robert A.
Format Journal Article
LanguageEnglish
Published England Oxford University Press 01.02.2016
by American Association of Neuropathologists, Inc
Subjects
Age of Onset
Aged
Aged, 80 and over
alpha-Synuclein - biosynthesis
alpha-Synuclein - genetics
Alzheimer Disease - cerebrospinal fluid
Alzheimer Disease - genetics
Alzheimer Disease - pathology
Amino Acid Sequence
Amyloid beta-Peptides - biosynthesis
Amyloid beta-Peptides - genetics
Autopsy
Biomarkers - analysis
Cell Death
Entorhinal Cortex - pathology
Female
Frontotemporal Lobar Degeneration - cerebrospinal fluid
Frontotemporal Lobar Degeneration - genetics
Frontotemporal Lobar Degeneration - pathology
Gyrus Cinguli - pathology
Humans
Male
Middle Aged
Molecular Sequence Data
Neurocalcin - cerebrospinal fluid
Neurocalcin - genetics
Neurons - pathology
Original
tau Proteins - biosynthesis
tau Proteins - genetics
Frontotemporal lobar degeneration
Human postmortem brain tissue
Alzheimer disease
Visinin-like 1 protein (Vilip-1)
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Abstract Recent studies have implicated the neuronal calcium-sensing protein visinin-like 1 protein (Vilip-1) as a peripheral biomarker in Alzheimer disease (AD), but little is known about expression of Vilip-1 in the brains of patients with AD. We used targeted and quantitative mass spectrometry to measure Vilip-1 peptide levels in the entorhinal cortex (ERC) and the superior frontal gyrus (SF) from cases with early to moderate stage AD, frontotemporal lobar degeneration (FTLD), and cognitively and neuropathologically normal elderly controls. We found that Vilip-1 levels were significantly lower in the ERC, but not in SF, of AD subjects compared to normal controls. In FTLD cases, Vilip-1 levels in the SF were significantly lower than in normal controls. These findings suggest a unique role for cerebrospinal fluid Vilip-1 as a biomarker of ERC neuron loss in AD.
AbstractList Recent studies have implicated the neuronal calcium-sensing protein visinin-like 1 protein (Vilip-1) as a peripheral biomarker in Alzheimer disease (AD), but little is known about expression of Vilip-1 in the brains of patients with AD. We used targeted and quantitative mass spectrometry to measure Vilip-1 peptide levels in the entorhinal cortex (ERC) and the superior frontal gyrus (SF) from cases with early to moderate stage AD, frontotemporal lobar degeneration (FTLD), and cognitively and neuropathologically normal elderly controls. We found that Vilip-1 levels were significantly lower in the ERC, but not in SF, of AD subjects compared to normal controls. In FTLD cases, Vilip-1 levels in the SF were significantly lower than in normal controls. These findings suggest a unique role for cerebrospinal fluid Vilip-1 as a biomarker of ERC neuron loss in AD.
Recent studies have implicated the neuronal calcium-sensing protein visinin-like 1 protein (Vilip-1) as a peripheral biomarker in Alzheimer disease (AD), but little is known about expression of Vilip-1 in the brains of patients with AD. We used targeted and quantitative mass spectrometry to measure Vilip-1 peptide levels in the entorhinal cortex (ERC) and the superior frontal gyrus (SF) from cases with early to moderate stage AD, frontotemporal lobar degeneration (FTLD), and cognitively and neuropathologically normal elderly controls. We found that Vilip-1 levels were significantly lower in the ERC, but not in SF, of AD subjects compared to normal controls. In FTLD cases, Vilip-1 levels in the SF were significantly lower than in normal controls. These findings suggest a unique role for cerebrospinal fluid Vilip-1 as a biomarker of ERC neuron loss in AD.Recent studies have implicated the neuronal calcium-sensing protein visinin-like 1 protein (Vilip-1) as a peripheral biomarker in Alzheimer disease (AD), but little is known about expression of Vilip-1 in the brains of patients with AD. We used targeted and quantitative mass spectrometry to measure Vilip-1 peptide levels in the entorhinal cortex (ERC) and the superior frontal gyrus (SF) from cases with early to moderate stage AD, frontotemporal lobar degeneration (FTLD), and cognitively and neuropathologically normal elderly controls. We found that Vilip-1 levels were significantly lower in the ERC, but not in SF, of AD subjects compared to normal controls. In FTLD cases, Vilip-1 levels in the SF were significantly lower than in normal controls. These findings suggest a unique role for cerebrospinal fluid Vilip-1 as a biomarker of ERC neuron loss in AD.
Author Ding, Ying
Kirkwood, Caitlin M.
Vatsavayi, Anil V.
MacDonald, Matthew L.
Koppel, Jeremy L.
Sweet, Robert A.
Schempf, Tadhg A.
Kofler, Julia K.
Ikonomovic, Milos D.
Sun, Mai
Lopez, Oscar L.
Yates, Nathan A.
AuthorAffiliation From the Translational Neuroscience Program (CMK, MLM, TAS, RAS), Department of Psychiatry (CMK, MLM, TAS, MDI, OLL, RAS), Department of Neurology (MDI, OLL, RAS), Department of Pathology (JKK), Biomedical Mass Spectrometry Center (MLM, YD, MS, NAY), Department of Cell Biology (CMK, NAY), University of Pittsburgh Schools of the Health Sciences, Pittsburgh, Pennsylvania; Mental Illness Research, Education, and Clinical Center (RAS), Geriatric Research Education and Clinical Center (MDI), VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania; Department of Psychiatry (AVV), University of Massachusetts School of Medicine, Worcester, Massachusetts; The Litwin-Zucker Research Center for the Study of Alzheimerʼs Disease (JLK), The Feinstein Institute for Medical Research (JLK), Manhasset, New York; The Zucker Hillside Hospital (JLK), The North-Shore LIJ Health System, Glen Oaks, New York
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  organization: From the Translational Neuroscience Program (CMK, MLM, TAS, RAS), Department of Psychiatry (CMK, MLM, TAS, MDI, OLL, RAS), Department of Neurology (MDI, OLL, RAS), Department of Pathology (JKK), Biomedical Mass Spectrometry Center (MLM, YD, MS, NAY), Department of Cell Biology (CMK, NAY), University of Pittsburgh Schools of the Health Sciences, Pittsburgh, Pennsylvania; Mental Illness Research, Education, and Clinical Center (RAS), Geriatric Research Education and Clinical Center (MDI), VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania; Department of Psychiatry (AVV), University of Massachusetts School of Medicine, Worcester, Massachusetts; The Litwin-Zucker Research Center for the Study of Alzheimer's Disease (JLK), The Feinstein Institute for Medical Research (JLK), Manhasset, New York; The Zucker Hillside Hospital (JLK), The North-Shore LIJ Health System, Glen Oaks, New York
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  fullname: Ikonomovic, Milos D.
  organization: From the Translational Neuroscience Program (CMK, MLM, TAS, RAS), Department of Psychiatry (CMK, MLM, TAS, MDI, OLL, RAS), Department of Neurology (MDI, OLL, RAS), Department of Pathology (JKK), Biomedical Mass Spectrometry Center (MLM, YD, MS, NAY), Department of Cell Biology (CMK, NAY), University of Pittsburgh Schools of the Health Sciences, Pittsburgh, Pennsylvania; Mental Illness Research, Education, and Clinical Center (RAS), Geriatric Research Education and Clinical Center (MDI), VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania; Department of Psychiatry (AVV), University of Massachusetts School of Medicine, Worcester, Massachusetts; The Litwin-Zucker Research Center for the Study of Alzheimer's Disease (JLK), The Feinstein Institute for Medical Research (JLK), Manhasset, New York; The Zucker Hillside Hospital (JLK), The North-Shore LIJ Health System, Glen Oaks, New York
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– sequence: 9
  givenname: Julia K.
  surname: Kofler
  fullname: Kofler, Julia K.
  organization: From the Translational Neuroscience Program (CMK, MLM, TAS, RAS), Department of Psychiatry (CMK, MLM, TAS, MDI, OLL, RAS), Department of Neurology (MDI, OLL, RAS), Department of Pathology (JKK), Biomedical Mass Spectrometry Center (MLM, YD, MS, NAY), Department of Cell Biology (CMK, NAY), University of Pittsburgh Schools of the Health Sciences, Pittsburgh, Pennsylvania; Mental Illness Research, Education, and Clinical Center (RAS), Geriatric Research Education and Clinical Center (MDI), VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania; Department of Psychiatry (AVV), University of Massachusetts School of Medicine, Worcester, Massachusetts; The Litwin-Zucker Research Center for the Study of Alzheimer's Disease (JLK), The Feinstein Institute for Medical Research (JLK), Manhasset, New York; The Zucker Hillside Hospital (JLK), The North-Shore LIJ Health System, Glen Oaks, New York
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  givenname: Oscar L.
  surname: Lopez
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  surname: Sweet
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  email: sweetra@upmc.edu
  organization: From the Translational Neuroscience Program (CMK, MLM, TAS, RAS), Department of Psychiatry (CMK, MLM, TAS, MDI, OLL, RAS), Department of Neurology (MDI, OLL, RAS), Department of Pathology (JKK), Biomedical Mass Spectrometry Center (MLM, YD, MS, NAY), Department of Cell Biology (CMK, NAY), University of Pittsburgh Schools of the Health Sciences, Pittsburgh, Pennsylvania; Mental Illness Research, Education, and Clinical Center (RAS), Geriatric Research Education and Clinical Center (MDI), VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania; Department of Psychiatry (AVV), University of Massachusetts School of Medicine, Worcester, Massachusetts; The Litwin-Zucker Research Center for the Study of Alzheimer's Disease (JLK), The Feinstein Institute for Medical Research (JLK), Manhasset, New York; The Zucker Hillside Hospital (JLK), The North-Shore LIJ Health System, Glen Oaks, New York
BackLink https://www.ncbi.nlm.nih.gov/pubmed/26769253$$D View this record in MEDLINE/PubMed
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Copyright Published by Oxford University Press on behalf of the American Association of Neuropathologists, Inc. 2016. This work is written by US Government employees and is in the public domain in the US. 2016
2016 by American Association of Neuropathologists, Inc.
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Keywords Frontotemporal lobar degeneration
Human postmortem brain tissue
Alzheimer disease
Visinin-like 1 protein (Vilip-1)
Language English
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content type line 23
Supplementary Data can be found at http://www.jnen.oxfordjournals.org.
This work was supported by grants MH16804 (MLM), AG05133 (OLL), AG014449 (MDI), AG027224 (RAS), and VAPHS grant BX000542 (RAS). The Biomedical Mass Spectrometry Center and UPCI Cancer Proteomics Facility are supported in part by award P30CA047904. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health, the National Institutes of Health, the Department of Veterans Affairs, or the United States Government.The authors have no biomedical financial interests or potential conflicts of interest to disclose.
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PublicationTitle Journal of neuropathology and experimental neurology
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Snippet Recent studies have implicated the neuronal calcium-sensing protein visinin-like 1 protein (Vilip-1) as a peripheral biomarker in Alzheimer disease (AD), but...
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StartPage 175
SubjectTerms Age of Onset
Aged
Aged, 80 and over
alpha-Synuclein - biosynthesis
alpha-Synuclein - genetics
Alzheimer Disease - cerebrospinal fluid
Alzheimer Disease - genetics
Alzheimer Disease - pathology
Amino Acid Sequence
Amyloid beta-Peptides - biosynthesis
Amyloid beta-Peptides - genetics
Autopsy
Biomarkers - analysis
Cell Death
Entorhinal Cortex - pathology
Female
Frontotemporal Lobar Degeneration - cerebrospinal fluid
Frontotemporal Lobar Degeneration - genetics
Frontotemporal Lobar Degeneration - pathology
Gyrus Cinguli - pathology
Humans
Male
Middle Aged
Molecular Sequence Data
Neurocalcin - cerebrospinal fluid
Neurocalcin - genetics
Neurons - pathology
Original
tau Proteins - biosynthesis
tau Proteins - genetics
Title Altered Levels of Visinin-Like Protein 1 Correspond to Regional Neuronal Loss in Alzheimer Disease and Frontotemporal Lobar Degeneration
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