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O4‐08‐01: Intranasal Insulin‐ And Biomarker‐associated Improvement in Memory and Functional Status in Mild Cognitive Impairment and Alzheimer's Disease: Results of a Randomized, Double‐blind, Placebo‐controlled Pilot Trial
Author(s) -
Craft Suzanne,
Baker Laura D.,
Montine Thomas J.,
Zhang Jing,
Watson G. Stennis,
Plymate Stephen,
Tsai Elaine,
Callaghan Maureen,
Leverenz James,
Gerton Brooke,
Trittschuh Emily
Publication year - 2010
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2010.08.054
Subject(s) - medicine , placebo , insulin , dementia , alzheimer's disease , insulin degrading enzyme , oncology , disease , pathology , alternative medicine
protein is sufficient to cause neurodegeneration and dementia. Several lines of transgenic mice have been produced that express human mutant tau. We have produced a mouse line expressing human P301S tau under the control of the murine Thy1 promoter. These mice exhibit the essential features of tauopathies, including neurodegeneration and abundant hyperphosphorylated tau deposits. Objective: We aimed to determine whether neural precursor cell transplantation could prevent tau-related nerve cell death in P301S tau transgenic mice. Methods: Cell-death was identified in specific areas of the cerebral cortex by immunoistochemistry with anti-NeuN antibody, cresyl violet staining and cell counting. Mouse neural precursor cells were transplanted to one hemisphere of 2-month-old P301S tau mice and the effect of transplantation on nerve cell death was examined 1 and 3 months later. RT-PCR and immunohistochemistry were used to identify mRNA and protein changes in both transplanted cells and the cortical areawith neuronal cell death. Results: We show that the transgenic human mutant P301S tau mouse line exhibits an age-related, progressive frontal cortical neuron loss, especially in the superficial layers, along with increased astrogliosis and that focal transplantation of neural precursor cells that differentiate into glia or direct astrocyte implantation results in neuroprotection.Conclusions: Neural precursor cell implantation, resulting in glial cell differentiation, leads to the rescue of cortical neurons in P301S tau transgenic mice. This indicates that early cell transplantation can rescue neurons from tau-related nerve cell death; it suggests a beneficial role for glial cell-based repair in neurodegenerative diseases.