Proteomics Landscape of Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is the most prevalent form of dementia, and the numbers of AD patients are expected to increase as human life expectancy improves. Deposition of β-amyloid protein (Aβ) in the extracellular matrix and intracellular neurofibrillary tangles are molecular hallmarks of the disease. Since the precise pathophysiology of AD has not been elucidated yet, effective treatment is not available. Thus, understanding the disease pathology, as well as identification and development of valid biomarkers, is imperative for early diagnosis as well as for monitoring disease progression and therapeutic responses. Keeping this goal in mind several studies using quantitative proteomics platform have been carried out on both clinical specimens including the brain, cerebrospinal fluid (CSF), plasma and on animal models of AD. In this review, we summarize the mass spectrometry (MS)-based proteomics studies on AD and discuss the discovery as well as validation stages in brief to identify candidate biomarkers.

Characterization of Cystatin B Interactome in Saliva from Healthy Elderly and Alzheimer’s Disease Patients

“…The results obtained in this explorative AP-MS study represent a starting point for next proteomic investigations, supported by technical verification with immunological techniques, to be performed on a larger cohort of patients at different stages of the disease progression and on other neurodegenerative diseases. It has been repeatedly stressed by various research groups that understanding the events responsible for AD pathogenesis requires the use of different proteomic strategies [ 17 , 18 , 20 , 42 ]; as suggested by Jain AP et al the understanding of molecular mechanisms and cellular signaling pathways involved in AD pathogenesis is needed for discovering new targets and developing new therapeutic strategies [ 20 ], as well as for the diagnostic and disease progression monitoring. To date, several proteomic studies have identified candidate biomarkers of AD in brain tissue and CSF [ 17 , 18 , 20 , 42 ].…”

“…All these diagnostic tools are limited by their costs (PET- and brain-MRI), and complexity, or invasiveness (CSF study). Many peripheral diagnostic biomarkers have been proposed, but still none have shown to be sensitive and specific enough to be considered good candidates [ 18 , 19 , 20 ]. Therefore, it is a global challenge to find novel, peripheral potential biomarkers useful for developing effective screening methods for large-scale application.…”

“…These properties of cystatin B, our previous insights on salivary proteoforms of cystatin B associated with AD [ 14 , 15 ], and the relevance of the characterization of peripheral potential biomarkers and of their interactome in AD led us to investigate the possible involvement of cystatin B in a PPI network in the oral cavity. The feasibility, non-invasiveness, painlessness, and low-cost of collecting saliva make this biofluid an optimal choice to discover protein biomarkers useful for the diagnosis and risk assessment of several diseases, including AD [ 28 , 29 ], as opposed to blood and CSF [ 20 ]. Saliva contains proteins/peptides of both glandular and non-glandular origin, as well as proteins from blood and the CNS, and changes in the salivary proteome may reflect pathological conditions at the CNS level.…”

“…In addition, in AD patients, the function of the major salivary glands and their secretion can be altered [ 28 , 30 , 31 ]. Saliva is a biofluid that has been investigated in the AD field [ 14 , 15 , 28 , 30 , 31 ], and to date, several salivary biomarkers of AD have been studied by different approaches, even if with contrasting outcomes [ 20 , 28 , 31 , 32 ].…”

Proteomic Analysis of Hydromethylthionine in the Line 66 Model of Frontotemporal Dementia Demonstrates Actions on Tau-Dependent and Tau-Independent Networks

“…Clinical proteomics have been used for almost three decades to discover diagnostic markers in neurodegenerative disorders (see [11][12][13][14][15][16][17][18][19][20]). These studies concentrated on AD and have used brain tissue, cerebrospinal fluid and blood as substrates for analysis.…”