IGF1R and Alzheimer disease: However, reducing IGF signalling with IGF1R heterozygous knockout [52] or inhibition of IGF1R with picropodophyllin that crosses the BBB, attenuates Aβ accumulation [53] and, when APP/PSEN1 mice are crossed with neuronal IGF1R knockout, Aβ accumulation and neuroinflammation are reduced and differential gene expression associated with AD is reversed [54,55].