Dephosphorylation of phosphorylated Tau (pTau)
protein, which is essential for the preservation of neuronal microtubule assemblies and for protection against
trauma-induced
tauopathy and
chronic traumatic encephalopathy (CTE), is primarily achieved in brain by tissue non-specific
alkaline phosphatase (TNAP). Paired helical filaments (PHFs) and Tau isolated from
Alzheimer's disease (AD) patients' brains have been shown to form microtubule assemblies with
tubulin only
after treatment with TNAP or
protein phosphatase-2A, 2B and -1, suggesting that
Tau protein in the PHFs of neurons in AD brain is hyperphosphorylated, which prevents microtubule assembly. Using blast or weight drop models of
traumatic brain injury (TBI) in rats, we observed pTau accumulation in the brain as early as 6h post-injury and further accumulation which varied regionally by 24h post-injury. The pTau accumulation was accompanied by reduced TNAP expression and activity in these brain regions and a significantly decreased plasma total
alkaline phosphatase activity after the weight drop. These results reveal that both blast- and impact acceleration-induced
head injuries cause an acute decrease in the level/activity of TNAP in the brain, which potentially contributes to
trauma-induced accumulation of pTau and the resultant
tauopathy. The regional changes in the level/activity of TNAP or accumulation of pTau after these
injuries did not correlate with the accumulation of
amyloid precursor
protein, suggesting that the basic mechanism underlying
tauopathy in TBI might be distinct from that associated with AD.