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Brain-related proteins as potential CSF biomarkers of Alzheimer's disease: A targeted mass spectrometry approach.
J Proteomics. 2018 06 30; 182:12-20.JP

Abstract

Alzheimer's disease (AD) is the most common cause of dementia, characterized by progressive cognitive decline. The main disease hallmarks include amyloid beta aggregates and neurofibrillary tangles. Brain pathology is reflected in cerebrospinal fluid (CSF); the core biomarkers amyloid beta 1-42, total and phosphorylated tau protein levels are changed, relative to cognitively normal elderly. Still, there is a need for additional biomarkers which could identify disease more accurately and at an earlier stage, predict severity and be used in research settings. Here we evaluated 30 brain-related proteins as candidate biomarkers of AD. Proteins were quantified in CSF samples from cognitively healthy individuals (n = 23) and patients with mild cognitive impairment (MCI) due to AD (n = 20) or dementia due to AD (n = 10) using selected reaction monitoring mass spectrometry assays. APLP1 protein was increased in MCI relative to control (p < 0.001). The best discrimination between MCI vs. controls was observed with a model combining APLP1 and SPP1 proteins (area under the curve, AUC = 0.84). The strongest associations between protein abundance and disease severity were found for APLP1, CNTN2 and SPP1 proteins, which had a significant correlation with MMSE and CDR tests (p < 0.05). This study identifies new proteins with biomarker potential at various stages of AD severity.

SIGNIFICANCE

The current study evaluated 30 brain-related, highly specific proteins as candidate biomarkers of AD diagnosis. Protein APLP1 showed promise as early AD biomarker; protein panel APLP1 and SPP1 had the best diagnostic potential in discriminating MCI from control group, while proteins APLP1, SPP1 and CNTN2 may be indicators of disease progression, demonstrating weak to moderate correlation with cognitive tests. This study therefore identifies new proteins with biomarker potential at early AD stage. If the performance of proposed biomarkers is further confirmed, these proteins may add value in the clinic or clinical trial settings as diagnostic biomarkers (alone or in combination with the existing biomarkers) of the prodromal AD stage, and in monitoring disease progression.

Authors+Show Affiliations

Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada; Department of Pathology & Laboratory Medicine, Mount Sinai Hospital, Toronto, Canada.Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada; Department of Pathology & Laboratory Medicine, Mount Sinai Hospital, Toronto, Canada; Department of Clinical Biochemistry, University Health Network, Toronto, Canada.Department of Biostatistics, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.Laboratory of Medicine, Department of Clinical Biochemistry, Hospital Universitario Central, Oviedo, Spain.Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.Department of Obstetrics and Gynecology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.Department of Pathology & Laboratory Medicine, Mount Sinai Hospital, Toronto, Canada.Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada; Department of Pathology & Laboratory Medicine, Mount Sinai Hospital, Toronto, Canada; Department of Clinical Biochemistry, University Health Network, Toronto, Canada. Electronic address: Eleftherios.Diamandis@sinaihealthsystem.ca.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29684683

Citation

Begcevic, Ilijana, et al. "Brain-related Proteins as Potential CSF Biomarkers of Alzheimer's Disease: a Targeted Mass Spectrometry Approach." Journal of Proteomics, vol. 182, 2018, pp. 12-20.
Begcevic I, Brinc D, Brown M, et al. Brain-related proteins as potential CSF biomarkers of Alzheimer's disease: A targeted mass spectrometry approach. J Proteomics. 2018;182:12-20.
Begcevic, I., Brinc, D., Brown, M., Martinez-Morillo, E., Goldhardt, O., Grimmer, T., Magdolen, V., Batruch, I., & Diamandis, E. P. (2018). Brain-related proteins as potential CSF biomarkers of Alzheimer's disease: A targeted mass spectrometry approach. Journal of Proteomics, 182, 12-20. https://doi.org/10.1016/j.jprot.2018.04.027
Begcevic I, et al. Brain-related Proteins as Potential CSF Biomarkers of Alzheimer's Disease: a Targeted Mass Spectrometry Approach. J Proteomics. 2018 06 30;182:12-20. PubMed PMID: 29684683.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Brain-related proteins as potential CSF biomarkers of Alzheimer's disease: A targeted mass spectrometry approach. AU - Begcevic,Ilijana, AU - Brinc,Davor, AU - Brown,Marshall, AU - Martinez-Morillo,Eduardo, AU - Goldhardt,Oliver, AU - Grimmer,Timo, AU - Magdolen,Viktor, AU - Batruch,Ihor, AU - Diamandis,Eleftherios P, Y1 - 2018/04/22/ PY - 2017/12/07/received PY - 2018/03/15/revised PY - 2018/04/17/accepted PY - 2018/4/24/pubmed PY - 2019/10/23/medline PY - 2018/4/24/entrez KW - Alzheimer's disease KW - Biomarkers KW - Cerebrospinal fluid KW - Mass spectrometry KW - Selected reaction monitoring SP - 12 EP - 20 JF - Journal of proteomics JO - J Proteomics VL - 182 N2 - : Alzheimer's disease (AD) is the most common cause of dementia, characterized by progressive cognitive decline. The main disease hallmarks include amyloid beta aggregates and neurofibrillary tangles. Brain pathology is reflected in cerebrospinal fluid (CSF); the core biomarkers amyloid beta 1-42, total and phosphorylated tau protein levels are changed, relative to cognitively normal elderly. Still, there is a need for additional biomarkers which could identify disease more accurately and at an earlier stage, predict severity and be used in research settings. Here we evaluated 30 brain-related proteins as candidate biomarkers of AD. Proteins were quantified in CSF samples from cognitively healthy individuals (n = 23) and patients with mild cognitive impairment (MCI) due to AD (n = 20) or dementia due to AD (n = 10) using selected reaction monitoring mass spectrometry assays. APLP1 protein was increased in MCI relative to control (p < 0.001). The best discrimination between MCI vs. controls was observed with a model combining APLP1 and SPP1 proteins (area under the curve, AUC = 0.84). The strongest associations between protein abundance and disease severity were found for APLP1, CNTN2 and SPP1 proteins, which had a significant correlation with MMSE and CDR tests (p < 0.05). This study identifies new proteins with biomarker potential at various stages of AD severity. SIGNIFICANCE: The current study evaluated 30 brain-related, highly specific proteins as candidate biomarkers of AD diagnosis. Protein APLP1 showed promise as early AD biomarker; protein panel APLP1 and SPP1 had the best diagnostic potential in discriminating MCI from control group, while proteins APLP1, SPP1 and CNTN2 may be indicators of disease progression, demonstrating weak to moderate correlation with cognitive tests. This study therefore identifies new proteins with biomarker potential at early AD stage. If the performance of proposed biomarkers is further confirmed, these proteins may add value in the clinic or clinical trial settings as diagnostic biomarkers (alone or in combination with the existing biomarkers) of the prodromal AD stage, and in monitoring disease progression. SN - 1876-7737 UR - https://www.unboundmedicine.com/medline/citation/29684683/Brain_related_proteins_as_potential_CSF_biomarkers_of_Alzheimer's_disease:_A_targeted_mass_spectrometry_approach_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1874-3919(18)30186-6 DB - PRIME DP - Unbound Medicine ER -