Insulin-like growth factor-I and its receptor in normal human and Alzheimer's disease brains

Evidence indicates that levels of insulin-like growth factor-I (IGF-I) are elevated in the serum of Alzheimer's disease patients. In the present study, using membrane binding assays, we have shown that [125I]IGF-I receptor binding sites are not significantly altered in the frontal cortex, hippocampus and cerebellum of the AD brain. However, in vitro receptor autoradiography revealed significant increases in the density of [125I]IGF-I receptor binding sites in layer IV of the frontal cortex, the stratum oriens of the hippocampus and the putamen nucleus of the striatum but not in other regions of the AD brain. IGF-I immunoreactivity was evident in the pyramidal neurons of the frontal cortex, pyramidal layer of CA1--CA4 subfields and the hilar neurons of the hippocampus, as well as the Purkinje cells of the cerebellum in control and AD brains. Additionally, in the AD brain, IGF-I immunoreacitivity was also observed to be localized with Abeta-containing diffuse and neuritic plaques as well as in astrocytes in the gray matter of the cortex and the hippocampus. These findings, taken together, indicate that although no striking alterations have been found in the number of IGF-I receptors or the peptide itself in the AD brain, the presence of immunoreactive IGF-I in the neuritic plaques suggests a putative role for the growth factor in AD pathology