Tau associated peripheral and central neurodegeneration: Identification of an early imaging marker for tauopathy

Pathological hyperphosphorylated tau is a key feature of Alzheimer's disease (AD) and Frontotemporal dementia (FTD). Using transgenic mice overexpressing human non-mutated tau (htau mice), we assessed the contribution of tau to peripheral and central neurodegeneration. Indices of peripheral small and large fiber neuropathy and learning and memory performances were assessed at 3 and 6 months of age. Overexpression of human tau is associated with peripheral neuropathy at 6 months of age. Our study also provides evidence that non-mutated tau hyperphosphorylation plays a critical role in memory deficits. In addition, htau mice had reduced stromal corneal nerve length with preservation of sub-basal corneal nerves, consistent with a somatofugal degeneration. Corneal nerve degeneration occurred prior to any cognitive deficits and peripheral neuropathy. Stromal corneal nerve loss was observed in patients with FTD but not AD. Corneal confocal microscopy may be used to identify early neurodegeneration and differentiate FTD from AD.

Automated summary

This study using htau mice model demonstrates that hyperphosphorylation of non-mutated tau leads to peripheral neuropathy and memory deficits, as well as corneal nerve degeneration. Corneal nerve degeneration precedes cognitive deficits and peripheral neuropathy, serving as a potential tool for distinguishing FTD from AD.