[HTML][HTML] Cerebrospinal fluid–based kinetic biomarkers of axonal transport in monitoring neurodegeneration
P Fanara, PYA Wong, KH Husted, S Liu… - The Journal of …, 2012 - Am Soc Clin Investig
P Fanara, PYA Wong, KH Husted, S Liu, VM Liu, LA Kohlstaedt, T Riiff, JC Protasio, D Boban…
The Journal of clinical investigation, 2012•Am Soc Clin InvestigProgress in neurodegenerative disease research is hampered by the lack of biomarkers of
neuronal dysfunction. We here identified a class of cerebrospinal fluid–based (CSF-based)
kinetic biomarkers that reflect altered neuronal transport of protein cargo, a common feature
of neurodegeneration. After a pulse administration of heavy water (2H2O), distinct, newly
synthesized 2H-labeled neuronal proteins were transported to nerve terminals and secreted,
and then appeared in CSF. In 3 mouse models of neurodegeneration, distinct 2H-cargo …
neuronal dysfunction. We here identified a class of cerebrospinal fluid–based (CSF-based)
kinetic biomarkers that reflect altered neuronal transport of protein cargo, a common feature
of neurodegeneration. After a pulse administration of heavy water (2H2O), distinct, newly
synthesized 2H-labeled neuronal proteins were transported to nerve terminals and secreted,
and then appeared in CSF. In 3 mouse models of neurodegeneration, distinct 2H-cargo …
Progress in neurodegenerative disease research is hampered by the lack of biomarkers of neuronal dysfunction. We here identified a class of cerebrospinal fluid–based (CSF-based) kinetic biomarkers that reflect altered neuronal transport of protein cargo, a common feature of neurodegeneration. After a pulse administration of heavy water (2H2O), distinct, newly synthesized 2H-labeled neuronal proteins were transported to nerve terminals and secreted, and then appeared in CSF. In 3 mouse models of neurodegeneration, distinct 2H-cargo proteins displayed delayed appearance and disappearance kinetics in the CSF, suggestive of aberrant transport kinetics. Microtubule-modulating pharmacotherapy normalized CSF-based kinetics of affected 2H-cargo proteins and ameliorated neurodegenerative symptoms in mice. After 2H2O labeling, similar neuronal transport deficits were observed in CSF of patients with Parkinson’s disease (PD) compared with non-PD control subjects, which indicates that these biomarkers are translatable and relevant to human disease. Measurement of transport kinetics may provide a sensitive method to monitor progression of neurodegeneration and treatment effects.
The Journal of Clinical Investigation