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

Neurobiology of Disease

Christopher Kobylecki¹  Andrew Marshall¹  Corinne G. Jolivalt²  Sze Hway Lim³  Rayaz A. Malik³  Matthew Jones³  Monty Silverdale³  Xiajun Zhou⁴  Katie E. Frizzi⁴  Morgan Cundiff⁴  Isabel Constantino⁴  Alexandra Marquez⁴  Nabeel Muttalib⁴  Lucie S. Guernsey⁴  Fernanda Arenas⁴  Maryam Ferdousi⁵  Georgios Ponirakis⁶ 

[1] Manchester Academic Health Sciences Centre, University of Manchester, UK;Department of Clinical Neurophysiology, Salford Royal Hospital, National Health Service Foundation Trust, Institute of Brain, Behaviour and Mental Health, University of Manchester, Manchester, UK;Department of Neurology, Manchester Centre for Clinical Neurosciences, Salford Royal NHS Foundation Trust, Salford, UK;Department of Pathology, University of California San Diego, USA;Institute of Cardiovascular Sciences, University of Manchester and Central Manchester NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK;Weill Cornell Medicine-Qatar, Doha, Qatar;

关键词: Corneal confocal microscopy;    Memory deficits;    Neurodegeneration;    Peripheral neuropathy;    Tau;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown