Abstract:
Alzheimer‘s disease (AD) is a debilitating neurodegenerative disease and the most common cause of dementia around the world. The disease is primarily characterized by synaptic degeneration, toxic level of amyloid beta peptides and tau neurofibrillary tangles forming aggregates in the brain. Neuroimaging modalities and body fluids, like blood (serum and plasma) and cerebrospinal fluid (CSF) are the key areas that are being targeted in search of biomarkers for diagnosis, prognosis, testing therapeutic strategies and response to these therapeutic interventions. However, the heterogeneity and multifactorial nature of the disease have rendered many of the reported biomarkers insufficient for clinical use. Since a well-established biomarker with the required level of specificity and sensitivity is lacking, our study focuses on finding a proteomic signature to overcome these issues. We utilized differential proteomic analysis on two datasets of CSF and blood samples (acquired from ADNI and ANM respectively), to uncover a proteomic signature that can diagnose AD and its prodromal stage, MCI. The proteins identified as significantly up-regulated were then validated by ELISA and Mass Spectrometry in the lab. A proteomic signature of four up-regulated proteins was acquired from the two datasets. APOE4 protein was found to be significantly up-regulated in AD and MCI in the CSF samples while Serum Amyloid A-1/A-2 (SAA1/2) was significantly up-regulated in AD and MCI in the blood samples. Lastly, Peptidoglycan Recognition protein (PGLYRP1) and Collagen Alpha-1 (VIII) chain (COL8A1) were significantly up-regulated only in AD of the blood samples while showing no change in MCI samples. COL8A1 protein was validated as a protein with significantly high expression by Mass Spectrometry and Elisa results. The proteins in the acquired signature perform various functions such as lipid metabolism, neuroinflammation and enhancing immunity against cancers and microbial infections. Except, APOE4, which is involved in fat metabolism and is a well-established risk factor for Alzheimer‘s disease, the other three proteins have not been studied for their role in progression or prevention of AD.
