Cerebrospinal fluid–based kinetic biomarkers of axonal transport in monitoring neurodegeneration
Patrizia Fanara, Po-Yin A. Wong, Kristofor H. Husted, Shanshan Liu, Victoria M. Liu, Lori A. Kohlstaedt, Timothy Riiff, Joan C. Protasio, Drina Boban, Salena Killion, Maudi Killian, Lorrie Epling, Elisabeth Sinclair, Julia Peterson, Richard W. Price, Deborah E. Cabin, Robert L. Nussbaum, Jörg Brühmann, Roland Brandt, Chadwick W. Christine, Michael J. Aminoff, Marc K. Hellerstein
Patrizia Fanara, Po-Yin A. Wong, Kristofor H. Husted, Shanshan Liu, Victoria M. Liu, Lori A. Kohlstaedt, Timothy Riiff, Joan C. Protasio, Drina Boban, Salena Killion, Maudi Killian, Lorrie Epling, Elisabeth Sinclair, Julia Peterson, Richard W. Price, Deborah E. Cabin, Robert L. Nussbaum, Jörg Brühmann, Roland Brandt, Chadwick W. Christine, Michael J. Aminoff, Marc K. Hellerstein
View: Text | PDF
Technical Advance

Cerebrospinal fluid–based kinetic biomarkers of axonal transport in monitoring neurodegeneration

Abstract

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.

Authors

Patrizia Fanara, Po-Yin A. Wong, Kristofor H. Husted, Shanshan Liu, Victoria M. Liu, Lori A. Kohlstaedt, Timothy Riiff, Joan C. Protasio, Drina Boban, Salena Killion, Maudi Killian, Lorrie Epling, Elisabeth Sinclair, Julia Peterson, Richard W. Price, Deborah E. Cabin, Robert L. Nussbaum, Jörg Brühmann, Roland Brandt, Chadwick W. Christine, Michael J. Aminoff, Marc K. Hellerstein

×
Problems with a PDF?

This file is in Adobe Acrobat (PDF) format. If you have not installed and configured the Adobe Acrobat Reader on your system.

Having trouble reading a PDF?

PDFs are designed to be printed out and read, but if you prefer to read them online, you may find it easier if you increase the view size to 125%.

Having trouble saving a PDF?

Many versions of the free Acrobat Reader do not allow Save. You must instead save the PDF from the JCI Online page you downloaded it from. PC users: Right-click on the Download link and choose the option that says something like "Save Link As...". Mac users should hold the mouse button down on the link to get these same options.

Having trouble printing a PDF?

  1. Try printing one page at a time or to a newer printer.
  2. Try saving the file to disk before printing rather than opening it "on the fly." This requires that you configure your browser to "Save" rather than "Launch Application" for the file type "application/pdf", and can usually be done in the "Helper Applications" options.
  3. Make sure you are using the latest version of Adobe's Acrobat Reader.

Supplemental data - Download (1.69 MB)

Advertisement