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Peripheral Protein Aggregates As Biomarkers For Neurodegenerative Diseases | 105564
Journal of Alzheimers Disease & Parkinsonism
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Neurodegenerative diseases such as Parkinson’s disease (PD) and Alzheimer’s
disease (AD) are characterized by the deposition of misfolded protein aggregates
in the central nervous system (CNS). Previous efforts have focused on the development
of CNS-proximal clinical biomarkers, including PET neuroimaging and cerebrospinal
fluid measures of alpha-synuclein, beta-amyloid and tau. However, these diagnostic
techniques are often used in clinical studies on patients with advanced disease state,
and are complex, invasive or expensive. Therefore, there remains an urgent need for
reliable, inexpensive and minimally invasive peripheral biomarkers. Recent studies
have revealed widespread peripheral involvement of PD- and AD-like pathology, often
prior to clinical manifestations of the diseases. Indeed, alpha-synuclein and tau deposits
have been observed in peripheral tissues in PD and AD, respectively. A formidable
challenge is that the levels of these amyloidogenic protein aggregates in peripheral
tissues are extremely low and thus only variably detectable using immunological
methods. Therefore, highly sensitive analytical platforms are required as the new
generation of biomarker assays specific for protein aggregates and amyloid fibrils.
The real-time quaking induced conversion (RT-QuIC) has emerged as a robust, rapid
and ultrasensitive technology for template-assisted amplification of misfolded protein
aggregates in neurodegenerative diseases. Using the RT-QuIC technique, our recent
studies have shown that disease-associated protein aggregates are readily detectable in
peripheral tissues of patients affected by PD, dementia with Lewy bodies, and AD and
other tauopathies. Validation of peripheral protein biomarkers will enable sensitive
premortem diagnostic tests for PD, AD, and related disorders, and accelerate clinical
trials for disease-modifying therapies.
Shu G Chen has received his PhD in 1992 from the State University of New York at Buffalo, New York, USA. He is an Associate Professor of Pathology and Neurology at Case Western Reserve University School of Medicine. His research centers on pathogenesis of Parkinson’s disease, Alzheimer’s disease and other neurodegenerative disorders. He has published more than 80 papers in scientific journals.