An immunohistochemical study of the distribution of brain-derived neurotrophic factor in the adult human brain, with particular reference to Alzheimer's disease

Brain-derived neurotrophic factor is a member of the family of neuronal dif ferentiation and survival-promoting molecules called neurotrophins. Neurona l populations known to show responsiveness to the action of brain-derived n eurotrophic factor include the cholinergic forebrain, mesencephalic dopamin ergic, cortical, hippocampal and striatal neurons. This fact has aroused co nsiderable interest in the possible contribution of an abnormal brain-deriv ed neurotrophic factor function to the aetiology and physiopathology of dif ferent neurodegenerative disorders, such as Alzheimer's disease. This repor t describes the cellular and regional distribution of brain-derived neurotr ophic factor in post mortem control human brain and in limited regions of t he brain in patients with Alzheimer's disease, as was revealed by immunohis tochemistry. Brain-derived neurotrophic factor is widely expressed in the control human brain, both by neurons and glia. In neurons, brain-derived neurotrophic fac tor was localized in the cell body, dendrites and axons. Among the structur es showing the most intense immunohistochemical labeling were the hippocamp us, claustrum, amygdala, bed nucleus of the stria terminalis, septum and th e nucleus of the solitary tract. In the striatum, immunoreactivity was more intense in striosomes than in the matrix. Many labeled neurons were found in the substantia nigra pars compacta. The large putatively cholinergic neu rons in the basal forebrain showed no immunoreactivity. The general pattern of labeling was similar in individuals with Alzheimer's disease. Brain-der ived neurotrophic factor-immunoreactive material was found in senile plaque s, and some immunoreactive cortical pyramidal neurons showed neurofibrillar y tangles, suggesting that brain-derived neurotrophic factor may be involve d in the process of neuronal degeneration and/or compensatory mechanisms wh ich occur in this illness. (C) 1998 IBRO. Published by Elsevier Science Ltd .