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

Background Deficits 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. Objective Strategies aimed at correcting deficits in Reelin might provide a novel therapeutic approach for AD. Methods Here, 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 . Results Incubation 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. Conclusions These 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.