PMID- 12456067 OWN - NLM STAT- MEDLINE DCOM- 20030110 LR - 20191025 IS - 0303-6995 (Print) IS - 0303-6995 (Linking) IP - 62 DP - 2002 TI - Neurotrophic factors and Alzheimer's disease: are we focusing on the wrong molecule? PG - 241-52 AB - Brain derived neurotrophic factor (BDNF) promotes cholinergic neuron function and survival. In Alzheimer's disease, BDNF mRNA and protein are decreased in basal forebrain cholinergic neuron target tissues such as cortex and hippocampus. Using RT-PCR, we demonstrate that BDNF is synthesized in basal forebrain, supplying cholinergic neurons with a local as well as a target-derived source of this factor. BDNF mRNA levels are decreased 50% in nucleus basalis of Alzheimer disease patients compared to controls. Thus, not only do the basal forebrain cholinergic neurons have a reduced supply of target-derived BDNF, but also of local BDNF. We also show by Western blotting that human CNS tissue contains both proBDNF and mature BDNF protein. Moreover, we demonstrate a significant (2.25-fold) deficit in proBDNF protein in Alzheimer's disease parietal cortex compared to controls. Thus, reduced BDNF mRNA and protein levels in Alzheimer's disease suggests that BDNF administration may be an effective therapeutic strategy for this disorder. FAU - Fahnestock, M AU - Fahnestock M AD - Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ont., Canada. fahnest@mcmaster.ca FAU - Garzon, D AU - Garzon D FAU - Holsinger, R M D AU - Holsinger RM FAU - Michalski, B AU - Michalski B LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Austria TA - J Neural Transm Suppl JT - Journal of neural transmission. Supplementum JID - 0425126 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Protein Precursors) RN - 0 (RNA, Messenger) SB - IM MH - Aged MH - Aged, 80 and over MH - Alzheimer Disease/*pathology/*physiopathology MH - Basal Nucleus of Meynert/physiology MH - Blotting, Western MH - Brain-Derived Neurotrophic Factor/analysis/*genetics MH - Humans MH - Middle Aged MH - Parietal Lobe/chemistry/pathology MH - Protein Precursors/analysis/genetics MH - RNA, Messenger/analysis MH - Reverse Transcriptase Polymerase Chain Reaction EDAT- 2002/11/29 04:00 MHDA- 2003/01/11 04:00 CRDT- 2002/11/29 04:00 PHST- 2002/11/29 04:00 [pubmed] PHST- 2003/01/11 04:00 [medline] PHST- 2002/11/29 04:00 [entrez] AID - 10.1007/978-3-7091-6139-5_22 [doi] PST - ppublish SO - J Neural Transm Suppl. 2002;(62):241-52. doi: 10.1007/978-3-7091-6139-5_22.