FK506 Reduces Amyloid Plaque Burden and Induces MMP-9 in A beta PP/PS1 Double Transgenic Mice

Deposition of amyloid-beta peptide (A beta) and neurofibrillary tangles are pathological hallmarks of Alzheimer's disease (AD), a neurodegenerative disease characterized by cognitive deficits and neuronal loss. Recently, calcineurin (CaN) has been reported as a potential modulator of memory function, synaptic plasticity, and neural degeneration in brains of AD animal models. In the present study, we examined the relationship between A beta accumulations and CaN activity in brains of the A beta PP/PS1 double transgenic mice. Treatment with FK506, a CaN inhibitor, significantly reduces A beta burden and restores synaptic proteins (synaptophysin and postsynaptic density protein-95; PSD-95) while inducing matrix metallopeptidase-9 (MMP-9) expression in GFAP-positive astrocytes in the brain. These results suggest a role of FK506 and control of CaN activity in neuroprotection associated with A beta deposition in AD.