This study investigates the role of tissue-nonspecific alkaline phosphatase (TNAP) in tauopathies. Researchers observed that TNAP is upregulated in the brains of Alzheimer's and Pick's disease patients, as well as in P301S tau transgenic mice. Genetic reduction of TNAP (haploinsufficiency) in P301S mice led to decreased neuronal hyperactivity, reduced brain atrophy, and improved survival. Pharmacological inhibition of TNAP with levamisole also ameliorated neurotoxicity and extended lifespan in these mice.
TNAP upregulation contributes to tau-induced neurotoxicity; its genetic or pharmacological inhibition reduces neurodegeneration and extends lifespan in tauopathy models.
P301S tau transgenic mice with TNAP haploinsufficiency (TNAP+/−) and P301S mice treated with the TNAP inhibitor levamisole to assess the impact of TNAP activity on tauopathy progression.
Neurodegeneration, Tauopathies, Alzheimer's disease, TNAP inhibition, Therapeutic intervention
Transgenic model, Haploinsufficiency, Pharmacological inhibition, P301S tauopathy model
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