Our results demonstrate altered active IGF1 and IGF1R levels in AD hippocampi, and suggest that boosting brain expression of IGF1 may comprise an approach to prevent neuronal damage and memory loss in AD.
These findings suggest that activation of IGF1R/CaMKIV/HAT/BDNF signaling by gestational environment enrichment may serve as a promising strategy to delay AD progression.
Moreover, in Alzheimer's disease neurons, a high proportion of genes responding to Alzheimer's disease showed a reversed differential expression when IGF1R was deleted.
While these disturbances were mostly corrected by restoring receptor function, blockade of the IGF-I receptor exacerbated AD-like pathology in old mutant mice already affected of brain amyloidosis and cognitive derangement.
Further studies demonstrated that: 1) ChAT expression increases with insulin or IGF-I stimulation; 2) ChAT is expressed in insulin and IGF-I receptor-positive cortical neurons; and 3) ChAT co-localization in insulin or IGF-I receptor-positive neurons is reduced in AD.