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Semiquantitative proteomic analysis of human hippocampal tissues from Alzheimer’s disease and age-matched control brains

Ilijana Begcevic12, Hari Kosanam12, Eduardo Martínez-Morillo12, Apostolos Dimitromanolakis2, Phedias Diamandis1, Uros Kuzmanov12, Lili-Naz Hazrati13 and Eleftherios P Diamandis1245*

Author Affiliations

1 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada

2 Samuel Lunenfeld Research Institute, Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON, Canada

3 Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada

4 Department of Clinical Biochemistry, University Health Network, Toronto, ON, Canada

5 Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, 60 Murray St., Box 32, Floor 6, Rm. L6-201, Toronto, ON, M5T 3L9, Canada

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Clinical Proteomics 2013, 10:5  doi:10.1186/1559-0275-10-5

Published: 1 May 2013

Abstract

Background

Alzheimer’s disease (AD) is the most common type of dementia affecting people over 65 years of age. The hallmarks of AD are the extracellular deposits known as amyloid β plaques and the intracellular neurofibrillary tangles, both of which are the principal players involved in synaptic loss and neuronal cell death. Tau protein and Aβ fragment 1–42 have been investigated so far in cerebrospinal fluid as a potential AD biomarkers. However, an urgent need to identify novel biomarkers which will capture disease in the early stages and with better specificity remains. High-throughput proteomic and pathway analysis of hippocampal tissue provides a valuable source of disease-related proteins and biomarker candidates, since it represents one of the earliest affected brain regions in AD.

Results

In this study 2954 proteins were identified (with at least 2 peptides for 1203 proteins) from both control and AD brain tissues. Overall, 204 proteins were exclusively detected in AD and 600 proteins in control samples. Comparing AD and control exclusive proteins with cerebrospinal fluid (CSF) literature-based proteome, 40 out of 204 AD related proteins and 106 out of 600 control related proteins were also present in CSF. As most of these proteins were extracellular/secretory origin, we consider them as a potential source of candidate biomarkers that need to be further studied and verified in CSF samples.

Conclusions

Our semiquantitative proteomic analysis provides one of the largest human hippocampal proteome databases. The lists of AD and control related proteins represent a panel of proteins potentially involved in AD pathogenesis and could also serve as prospective AD diagnostic biomarkers.

Keywords:
Alzheimer’s disease; Cerebrospinal fluid; Hippocampus; Human brain; Mass spectrometry