Insulin-like growth factor-I and its receptor in the frontal cortex, hippocampus, and cerebellum of normal human and Alzheimer disease brains

Assimilated evidence indicates that the neurotoxic potential of amyloid bet a (A beta) peptide and an alteration in the level of growth factor(s) may p ossibly be involved in the loss of neurons observed in the brain of patient s suffering from Alzheimer disease (AD), the prevalent cause of dementia in the elderly. In the present study, using receptor binding assays and immun ocytochemistry, we evaluated the pharmacological profile of insulin-like gr owth factor-I (IGF-I) receptors and the distribution of IGF-I immunoreactiv ity in the frontal cortex, hippocampus, and cerebellum of AD and age-matche d control brains. In control brains, [I-125]IGF-I binding was inhibited mor e potently by IGF-I than by Des(1-3)IGF-I, IGF-II or insulin. The IC50 valu es for IGF-I in the frontal cortex, hippocampus, and cerebellum of the norm al brain did not differ significantly from the corresponding regions of the AD brain. Additionally, neither K-D nor B-max values were found to differ in the hippocampus of AD brains from the controls. At the regional levels, [I-125]IGF-I binding sites in the AD brain also remained unaltered compared to the controls. As for the peptide itself, IGF-I immunoreactivity, in nor mal control brains, was evident primarily in a subpopulation of astrocytes in the frontal cortex and hippocampus, and in certain Purkinje cells of the cerebellum. In AD brains, a subset of A beta -containing neuritic plaques, apart from astrocytes, exhibit IGF-I immunoreactivity. These results, take n together, suggest a role for ICF-I in compensatory plasticity and/or surv ival of the susceptible neurons in AD brains. (C) 2000 Wiley-Liss, Inc.