Quantitation of BDNF mRNA in human parietal cortex by competitive reverse transcription-polymerase chain reaction: decreased levels in Alzheimer's disease

Alzheimer's disease is a progressive neurodegenerative disorder of the cent ral nervous system. One pathological characteristic is excessive neuronal l oss in specific regions of the brain. Among the areas most severely affecte d are the basal forebrain cholinergic neurons and their projection regions, the hippocampus and cortex. Neurotrophic factors, particularly the neurotr ophins nerve growth factor and brain-derived neurotrophic factor, play an i mportant role in the development, regulation and survival of basal forebrai n cholinergic neurons. Furthermore, brain-derived neurotrophic factor regul ates the function of hippocampal and cortical neurons. Neurotrophins are sy nthesized in hippocampus and cortex and retrogradely transported to the bas al forebrain. Decreased levels of neurotrophic factors are suspected to be involved in the neurodegenerative changes observed in Alzheimer's disease. We examined autopsied parietal cortex samples from age- and gender-matched Alzheimer's diseased and neurologically non-impaired individuals using the quantitative technique of competitive RT-PCR. We demonstrate a 3.4-fold dec rease in brain-derived neurotrophic factor mRNA levels in the parietal cort ex of patients with Alzheimer's disease compared to controls (p < 0.004). A decrease in brain-derived neurotrophic factor synthesis could have detrime ntal effects on hippocampal, cortical and basal forebrain cholinergic neuro ns and may account for their selective vulnerability in Alzheimer's disease . (C) 2000 Elsevier Science B.V. All rights reserved.