Cis-p-tau plays crucial role in lysolecithin-induced demyelination and subsequent axonopathy in mouse optic chiasm.

Multiple sclerosis (MS) is an autoimmune demyelinating disease that leads to axon degeneration as the major cause of everlasting neurological disability. The cis-phosphorylated tau (cis-p-tau) is an isoform of tau phosphorylated on threonine 231 and causes tau fails to bind micro-tubules and promotes assembly. It gains toxic function and forms tangles in the cell which finally leads to cell death. An antibody raised against cis- p-tau (cis mAb) detects this isoform and induces its clearance. Here, we investigated the formation of cis-p-tau in a lysophosphatidylcholine (LPC)-induced prolonged demyelination model as well as the beneficial effects of its clearance using cis mAb. Cis -p-tau was increased in the lesion site, especially in axons and microglia. Behavioral and functional studies were performed using visual cliff test, visual placing test, and visual evoked potential recording. Cis-p-tau clearance resulted in decreased gliosis, protected myelin and reduced axon degeneration. Analysis of behavioral and electrophysiological data showed that clearance of cis-p-tau by cis mAb treatment improved the visual acuity along with the integrity of the optic pathway. Our results highlight the opportunity of using cis mAb as a new therapy for protecting myelin and axons in patients suffering from MS.