Immunocal®, a cysteine-rich whey protein, rescues reelin and reduces amyloid plaque burden in a transgenic amyloid-β protein precursor (hAβPPSweInd) mouse model of Alzheimer's disease.

Abstract

BackgroundDeficits in Reelin expression play a significant role in the pathogenesis of various neurological disorders, including schizophrenia and Alzheimer's disease (AD). Notably, Reelin-expressing neurons of the entorhinal cortex layer II are among the first to be affected in AD.ObjectiveStrategies aimed at correcting deficits in Reelin might provide a novel therapeutic approach for AD.MethodsHere, we examined the effects of the whey protein supplement and glutathione (GSH) precursor, Immunocal^®, on Reelin expression both in vitro in hippocampal-entorhinal cortex slices from rat brain and in vivo in the hAβPP_SweInd (J20) mouse model of AD.ResultsIncubation of brain slices with Immunocal^® increased Reelin expression at the mRNA and protein levels. Oral treatment with Immunocal^®, given ad libitum in drinking water beginning at 3 months of age, corrected a deficit in cortical GSH levels observed in untreated mice and preserved Reelin expression in the hippocampal-entorhinal cortex sub-region of 5-month-old J20 mice. We also assessed the long-term effects of Immunocal^® by treating J20 mice from 3 months old to 12 months old. Long-term Immunocal^® treatment preserved brain GSH and rescued Reelin mRNA and protein expression, while significantly reducing amyloid plaque formation in the entorhinal cortex and hippocampus of AD mice.ConclusionsThese findings suggest that Immunocal^® promotes Reelin expression in vitro and sustains brain GSH and Reelin expression while diminishing amyloid plaque load in the entorhinal cortex and hippocampus of J20 mice. Thus, Immunocal^® offers a promising therapeutic approach to enhance Reelin expression and curtail amyloid deposition in AD.