MAPT and Alzheimer disease: However, when crossed with TgF344-AD rats, lowering IGF-1 signaling per se failed to confer protection against AD-related pathology, including amyloid burden, phosphorylated tau or neuroinflammation in male and female TgF344-AD rats, and even appeared to exacerbate facets of disease in females, including an increase in cortical small amyloid plaques.