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

• Published in: Neurobiology of disease 2021-04, Vol.151, p.105273-105273, Article 105273
• Main Authors: Marquez, Alexandra, Guernsey, Lucie S., Frizzi, Katie E., Cundiff, Morgan, Constantino, Isabel, Muttalib, Nabeel, Arenas, Fernanda, Zhou, Xiajun, Lim, Sze Hway, Ferdousi, Maryam, Ponirakis, Georgios, Silverdale, Monty, Kobylecki, Christopher, Jones, Matthew, Marshall, Andrew, Malik, Rayaz A., Jolivalt, Corinne G.
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - diagnostic imaging; Alzheimer Disease - pathology; Animals; Cornea - diagnostic imaging; Cornea - pathology; Corneal confocal microscopy; Female; Frontotemporal Dementia - diagnostic imaging; Frontotemporal Dementia - pathology; Humans; Memory deficits; Memory Disorders - etiology; Mice; Mice, Transgenic; Microscopy, Confocal; Middle Aged; Nerve Degeneration - diagnostic imaging; Nerve Degeneration - pathology; Neurodegeneration; Peripheral Nervous System Diseases - diagnostic imaging; Peripheral Nervous System Diseases - pathology; Peripheral neuropathy; Tau; tau Proteins - metabolism; Tauopathies - diagnostic imaging; Tauopathies - pathology
• ISSN: 0969-9961; 1095-953X
• DOI: 10.1016/j.nbd.2021.105273

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.