Proteomic-based Signature of Brain-related Proteins as Novel Candidate Biomarkers for Alzheimer’s Disease Diagnosis

Alzheimer’s disease (AD) is the most common type of dementia characterized by the progressive memory loss and cognitive decline, with typical age of onset after 65 years. The main disease hallmarks include extracellular amyloid beta deposits and intracellular neurofibrillary tangles. Brain pathology is reflected in cerebrospinal fluid (CSF) where core biomarkers amyloid beta 1-42, total tau, and phosphorylated tau protein levels are changed relative to cognitively normal elderly. There is a need for novel disease-specific biomarkers that will capture disease more accurately and at an earlier stage, predict disease severity, and be used in research and clinical trial settings for patients’ enrichment and stratification or to monitor drug efficacy. The aim of the present dissertation is to evaluate diagnostic potential of brain-related proteins in CSF of AD patients. The study was focused on proteins with high specificity for brain tissue. Only proteins expressed predominantly in the brain and reliably identified in the human CSF proteome were selected for development of multiplex mass spectrometry-based assay. Candidate biomarkers were then evaluated in AD patients with different spectrum of disease severity and cognitively healthy individuals (in total 154 subjects). This exploratory study suggests APLP1 protein as a promising biomarker for early AD detection. Specifically, the protein was elevated in mild cognitive impairment compared to cognitively healthy individuals (p

Department dc:contributor.department

Laboratory Medicine and Pathobiology

Year dc:date.issued

2018

Author dc:creator

• Begcevic, Ilijana

Advisor dc:contributor.advisor

• Diamandis, Eleftherios P

• Alzheimer's disease
• Biomarkers
• Cerebrospinal fluid
• Mass spectrometry
• Selected reaction monitoring

Handle dc:identifier.uri

http://hdl.handle.net/1807/89665

OAI identifier oai:identifier

oai:utoronto.scholaris.ca:1807/89665