1. Tau associated peripheral and central neurodegeneration: Identification of an early imaging marker for tauopathy
- Author
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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, and Jolivalt, Corinne G
- Subjects
Biomedical and Clinical Sciences ,Ophthalmology and Optometry ,Aging ,Neurosciences ,Brain Disorders ,Alzheimer's Disease ,Acquired Cognitive Impairment ,Peripheral Neuropathy ,Alzheimer's Disease Related Dementias (ADRD) ,Rare Diseases ,Eye Disease and Disorders of Vision ,Physical Injury - Accidents and Adverse Effects ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Neurodegenerative ,Dementia ,Frontotemporal Dementia (FTD) ,Aetiology ,2.1 Biological and endogenous factors ,Neurological ,Alzheimer Disease ,Animals ,Cornea ,Female ,Frontotemporal Dementia ,Humans ,Memory Disorders ,Mice ,Mice ,Transgenic ,Microscopy ,Confocal ,Middle Aged ,Nerve Degeneration ,Peripheral Nervous System Diseases ,Tauopathies ,tau Proteins ,Corneal confocal microscopy ,Memory deficits ,Neurodegeneration ,Peripheral neuropathy ,Tau ,Clinical Sciences ,Neurology & Neurosurgery ,Biochemistry and cell biology - Abstract
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.
- Published
- 2021