Targeted mass spectrometry to quantify brain-derived cerebrospinal fluid biomarkers in Alzheimer's disease

Clinical Proteomics
Maotian ZhouNicholas T. Seyfried

Abstract

Alzheimer's disease (AD) is the most common cause of dementia, characterized by progressive cognitive decline. Protein biomarkers of AD brain pathology, including β-amyloid and Tau, are reflected in cerebrospinal fluid (CSF), yet the identification of additional biomarkers linked to other brain pathophysiologies remains elusive. We recently reported a multiplex tandem-mass tag (TMT) CSF proteomic analysis of nearly 3000 proteins, following depletion of highly abundant proteins and off-line fractionation, across control and AD cases. Of these, over 500 proteins were significantly increased or decreased in AD, including markers reflecting diverse biological functions in brain. Here, we use a targeted mass spectrometry (MS) approach, termed parallel reaction monitoring (PRM), to quantify select CSF biomarkers without pre-depletion or fractionation to assess the reproducibility of our findings and the specificity of changes for AD versus other causes of cognitive impairment. We nominated 41 proteins (94 peptides) from the TMT CSF discovery dataset, representing a variety of brain cell-types and biological functions, for label-free PRM analysis in a replication cohort of 88 individuals that included 20 normal controls, 37 clinically...Continue Reading

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Citations

Sep 9, 2020·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Sruti RayaproluNicholas T Seyfried
Nov 3, 2020·Critical Reviews in Clinical Laboratory Sciences·Diana Navas-CarrilloEsteban Orenes-Piñero
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Apr 4, 2021·Proteomes·Ankit P Jain, Gajanan Sathe
Apr 20, 2021·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Anuja Shreeram KulkarniKun Qian
May 14, 2021·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·David G Morgan, Michelle M Mielke

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Methods Mentioned

BETA
ELISA

Software Mentioned

GraphPad
GraphPad Prism
INNOTEST
WGCNA R package
MATLAB
Skyline

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