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We characterized the transport profiles in 3 transgenic mouse models carrying amyotrophic lateral sclerosis (ALS)\u2010associated genes, aging mice, and SOD1\n                      <jats:sup>G93A<\/jats:sup>\n                      transgenic mice following CRISPR\/Cas9 gene editing. Lastly, we studied the effect of prior immunization of tetanus toxoid on the transport profile of TTC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      This technique defines a quantitative profile of net retrograde axonal transport of TTC in living mice. The profile is distinctly abnormal in transgenic SOD1\n                      <jats:sup>G93A<\/jats:sup>\n                      mice as young as 65\u2009days (presymptomatic) and worsens with disease progression. Moreover, this method detects a distinct therapeutic benefit of gene editing in transgenic SOD1\n                      <jats:sup>G93A<\/jats:sup>\n                      mice well before other clinical parameters (eg, grip strength) show improvement. Symptomatic transgenic PFN1\n                      <jats:sup>C71G\/C71G<\/jats:sup>\n                      ALS mice display gross reductions in net retrograde axonal transport, which is also disturbed in asymptomatic mice harboring a human\n                      <jats:italic>C9ORF72<\/jats:italic>\n                      transgene with an expanded GGGGCC repeat motif. In wild\u2010type mice, net retrograde axonal transport declines with aging. Lastly, prior immunization with tetanus toxoid does not preclude use of this assay.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>This assay of net retrograde axonal transport has broad potential clinical applications and should be particularly valuable as a physiological biomarker that permits early detection of benefit from potential therapies for motor neuron diseases. ANN NEUROL 2022;91:716\u2013729<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.26329","type":"journal-article","created":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T02:44:35Z","timestamp":1645152275000},"page":"716-729","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Imaging Net Retrograde Axonal Transport In Vivo: A Physiological Biomarker"],"prefix":"10.1002","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3444-9696","authenticated-orcid":false,"given":"Pin\u2010Tsun Justin","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Neurology University of Massachusetts Chan Medical School  Worcester MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary","family":"Kennedy","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Massachusetts Chan Medical School  Worcester MA USA"},{"name":"RNA 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