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

NEUROBIOLOGY OF DISEASE

卷:151

Article

Marquez, Alexandra¹  Guernsey, Lucie S.¹  Frizzi, Katie E.¹  Cundiff, Morgan¹  Constantino, Isabel¹  Muttalib, Nabeel¹  Arenas, Fernanda¹  Zhou, Xiajun¹  Lim, Sze Hway²  Ferdousi, Maryam^4,5  Ponirakis, Georgios⁶  Silverdale, Monty^2,3  Kobylecki, Christopher^2,3  Jones, Matthew²  Marshall, Andrew⁷  Malik, Rayaz A.^4,8  Jolivalt, Corinne G.¹ 

[1] Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA

[2] Salford Royal NHS Fdn Trust, Manchester Ctr Clin Neurosci, Dept Neurol, Salford, Lancs, England

[3] Univ Manchester, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England

[4] Univ Manchester, Inst Cardiovasc Sci, Manchester, Lancs, England

[5] Cent Manchester NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England

[6] Weill Cornell Med Qatar, Doha, Qatar

[7] Univ Manchester, Dept Clin Neurophysiol, Salford Royal Hosp, Natl Hlth Serv Fdn Trust,Inst Brain Behav & Menta, Manchester, Lancs, England

[8] Weill Cornell Med Qatar, Dept Med, Doha, Qatar

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

DOI  :  10.1016/j.nbd.2021.105273

来源: Elsevier

【 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.