Neuroproteomics Chip-Based Mass Spectrometry and Other Techniques for Alzheimer’s Disease Biomarkers – Update

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disease of growing interest given that there is cognitive damage and symptom onset acceleration. Therefore, it is important to find AD biomarkers for early diagnosis, disease progression, and discrimination of AD and other diseases. Objective: The objective of this study is to update the relevance of mass spectrometry for the identification of peptides and proteins involved in AD useful as discriminating biomarkers. Methods: Proteomics and peptidomics technologies that show the highest possible specificity and selectivity for AD biomarkers are analyzed, together with the biological fluids used. In addition to positron emission tomography and magnetic resonance imaging, MALDI-TOF mass spectrometry is widely used to identify proteins and peptides involved in AD. The use of protein chips in SELDI technology and electroblotting chips for peptides makes feasible small amounts (μL) of samples for analysis. Results: Suitable biomarkers are related to AD pathology, such as intracellular neurofibrillary tangles; extraneuronal senile plaques; neuronal and axonal degeneration; inflammation and oxidative stress. Recently, peptides were added to the candidate list, which are not amyloid-β or tau fragments, but are related to coagulation, brain plasticity, and complement/neuroinflammation systems involving the neurovascular unit. Conclusion: The progress made in the application of mass spectrometry and recent chip techniques is promising for discriminating between AD, mild cognitive impairment, and matched healthy controls. The application of this technique to blood samples from patients with AD has shown to be less invasive and fast enough to determine the diagnosis, stage of the disease, prognosis, and follow-up of the therapeutic response.