Importantly, several studies have observed altered levels of IGFs and IGFBPs in the plasma and cerebrospinal fluid (CSF) of AD patients, further suggesting that the neuroprotective and synaptic maintenance effects elicited by IGF signaling may be altered in AD (Tham et al., 1993; Vardy et al., 2007; Salehi et al., 2008; Hertze et al., 2014; Åberg et al., 2015). Here, IGF1 is linked to Alzheimer disease.