Novel Diagnostic Applications for Disease-Associated aggregates of Parkinson's disease and Related Disorders

Project: Experimental Development/Translation Research

Project Details

Abstract

The diagnosis of common neurodegenerative diseases, such as Parkinson’s disease (PD), is mainly based on clinical symptoms, and can be inaccurate since this disease shares several similar clinical profiles with other neurodegenerative disorders. The main barrier we are facing is the lack of reliable biomarkers especially for preclinical stage of neurodegenerative disorders. One of the most prominent pathological features of all the major neurodegenerative diseases is deposition of specific protein aggregates in neurons and glia. In PD, dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), such aggregates are composed of the protein α-synuclein (α-syn) whose conformation is transformed to beta-sheet-rich structure in disease. Aggregation of α-syn protein with pathogenic conformation appears before the clinical onset of the disease, thus making these aggregates a strong candidate for biomarker and therapeutic target. Real-time quaking induced conversion (RT-QuIC) also known as seeding amplification assay (SAA), has shown significant sensitivity and specificity using cerebrospinal fluid (CSF) in differentiating PD, DLB and MSA from controls or other neurodegenerative diseases. Despite its high sensitivity, many limitations are associated and should be addressed. It remains unclear if SAA can be utilized in biofluids that are collected with less invasive methods than CSF, such as blood. An additional challenge is the semi-quantitative nature, lack of robustness and the lengthy process for conducting this assay. This project presents proof-of-concept data for a new approach that combines the seeding amplification process and quantitative, convenient nature of ELISA, termed the seeding amplification immunoassay (SAIA) using our novel monoclonal antibodies that are highly specific for pathogenic aggregate forms of α-syn with beta-sheet structure aiming for PD diagnosis and progression. This novel immunoassay (SAIA) will be conducted on human CSF and plasma samples from cross-sectional and longitudinal cohort studies of PD and healthy control subjects (Ctrl).

Submitting Institute Name

Hamad Bin Khalifa University (HBKU)
Sponsor's Award NumberARG01-0514-230148
Proposal IDEX-QNRF-ARG-10
StatusActive
Effective start/end date1/04/241/04/27

Collaborative partners

Primary Theme

  • None

Primary Subtheme

  • None

Secondary Theme

  • None

Secondary Subtheme

  • None

Keywords

  • Alpha-synuclein
  • Parkinon's disease
  • Beta-sheet structure

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