| First Author | Fanara P | Year | 2012 |
| Journal | J Clin Invest | Volume | 122 |
| Issue | 9 | Pages | 3159-69 |
| PubMed ID | 22922254 | Mgi Jnum | J:190745 |
| Mgi Id | MGI:5449647 | Doi | 10.1172/JCI64575 |
| Citation | Fanara P, et al. (2012) Cerebrospinal fluid-based kinetic biomarkers of axonal transport in monitoring neurodegeneration. J Clin Invest 122(9):3159-69 |
| abstractText | 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. |
