Protein signature in cerebrospinal fluid and serum of Alzheimer’s disease patients: The case of apolipoprotein A-1 proteoforms

Chiara Fania, Beatrice Arosio, Daniele Capitanio, Enrica Torretta, Cristina Gussago, Evelyn Ferri, Daniela Mari, Cecilia Gelfi

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

In the diagnosis of Alzheimer’s disease (AD) total tau (T-tau), tau phosphorylated at threonine 181 (P-tau181), and the 42 amino acid isoform of alpha β-amyloid (Aβ) are well established surrogate CSF markers. However, there is a constant need for new diagnostic markers to identify the disease at a very early stage. The identification of new molecules for AD diagnosis and monitoring in CSF is hampered by several “confounding” factors including intra- and inter-individual, pre-analytical and analytical variabilities. In an attempt to partially overcome patient’s variability and to determine new molecules significantly dysregulated in CSF, we assessed the proteome profile of low molecular weight protein species in CSF and serum of the same patients. CSFs and sera from 36 ADs, 32 iNPHs (idiopathic normal pressure hydrocephalus) and 12 controls were compared by MALDI profiling (non-parametric statistics, CV<20%, AUC>0.750). After protein identification by mass spectrometry, the proteoform composition was assessed by 2-D DIGE/MS. Results indicated that CSF of iNPH can be used as control. Serum and CSF of AD patients shows a specific protein profile compared to iNPH samples. A variation (p<0.01) of Apo A-1 levels in AD, together with a specific dysregulation of Apo A-1 proteoforms was observed. The profiling of CSF and serum of the same patients, suggests that the decrement of total Apo A-1 occurs specifically in CSF. Serum and CSF of AD shows a characteristic Apo A-1 proteoform pattern suggesting it as potential marker which can support the clinical workflow adopted for AD diagnosis and progression.

Original languageEnglish
Article numbere0179280
JournalPLoS One
Volume12
Issue number6
DOIs
Publication statusPublished - Jun 1 2017

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apolipoprotein A
Cerebrospinal fluid
Apolipoprotein A-I
cerebrospinal fluid
Alzheimer disease
Cerebrospinal Fluid
Alzheimer Disease
Normal Pressure Hydrocephalus
hydrocephalus
Serum
Proteins
valrubicin
proteins
disease diagnosis
disease surveillance
Workflow
Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
Threonine
Proteome
amyloid

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Protein signature in cerebrospinal fluid and serum of Alzheimer’s disease patients : The case of apolipoprotein A-1 proteoforms. / Fania, Chiara; Arosio, Beatrice; Capitanio, Daniele; Torretta, Enrica; Gussago, Cristina; Ferri, Evelyn; Mari, Daniela; Gelfi, Cecilia.

In: PLoS One, Vol. 12, No. 6, e0179280, 01.06.2017.

Research output: Contribution to journalArticle

Fania, Chiara ; Arosio, Beatrice ; Capitanio, Daniele ; Torretta, Enrica ; Gussago, Cristina ; Ferri, Evelyn ; Mari, Daniela ; Gelfi, Cecilia. / Protein signature in cerebrospinal fluid and serum of Alzheimer’s disease patients : The case of apolipoprotein A-1 proteoforms. In: PLoS One. 2017 ; Vol. 12, No. 6.
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