PMID- 15899246 OWN - NLM STAT- MEDLINE DCOM- 20050715 LR - 20151119 IS - 0014-4886 (Print) IS - 0014-4886 (Linking) VI - 194 IP - 1 DP - 2005 Jul TI - Decreased levels of BDNF protein in Alzheimer temporal cortex are independent of BDNF polymorphisms. PG - 91-6 AB - Levels of brain-derived neurotrophic factor (BDNF) are reduced in specific brain regions in Alzheimer's disease (AD) and BDNF gene polymorphisms have been suggested to influence AD risk, hippocampal function, and memory. We investigated whether the polymorphisms at the BDNF 196 and 270 loci were associated with AD in a clinical and neuropathological cohort of 116 AD cases and 77 control subjects. To determine how BDNF protein levels relate to BDNF polymorphisms and AD pathology, we also measured BDNF in temporal association cortex, frontal association cortex, and cerebellum in 57 of the AD and 21 control cases. BDNF protein levels in temporal neocortex of the AD brains were reduced by 33% compared to control brains, whereas levels were unchanged in frontal and cerebellar cortex. The BDNF genotypes were not significantly associated with a diagnosis of AD, although the BDNF 270 C allele was slightly overrepresented among carriers of the APOEepsilon4 allele. Moreover, BDNF protein levels did not differ between the various BDNF genotypes and alleles. Neuropathologically, the loss of BDNF in AD showed a weak correlation with accumulation of neuritic amyloid plaques and loss of the neuronal/synaptic marker synaptophysin. The results suggest that the investigated BDNF polymorphisms are neither robust genetic risk factors nor determinants of BDNF protein levels in AD. FAU - Lee, Jung AU - Lee J AD - Harvard Medical School, Massachusetts General Hospital, 114 16th Street, Charlestown, MA 02129, USA. FAU - Fukumoto, Hiroaki AU - Fukumoto H FAU - Orne, Jennifer AU - Orne J FAU - Klucken, Jochen AU - Klucken J FAU - Raju, Susan AU - Raju S FAU - Vanderburg, Charles R AU - Vanderburg CR FAU - Irizarry, Michael C AU - Irizarry MC FAU - Hyman, Bradley T AU - Hyman BT FAU - Ingelsson, Martin AU - Ingelsson M LA - eng GR - AG 05134/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Exp Neurol JT - Experimental neurology JID - 0370712 RN - 0 (Apolipoprotein E4) RN - 0 (Apolipoproteins E) RN - 0 (Biomarkers) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Synaptophysin) SB - IM MH - Aged MH - Alzheimer Disease/*genetics/*metabolism/pathology MH - Apolipoprotein E4 MH - Apolipoproteins E/genetics MH - Biomarkers/metabolism MH - Brain-Derived Neurotrophic Factor/*genetics/*metabolism MH - Cerebellum/metabolism MH - Cohort Studies MH - DNA Mutational Analysis MH - Down-Regulation/physiology MH - Female MH - Gene Frequency MH - Genetic Predisposition to Disease/genetics MH - Genetic Testing MH - Genotype MH - Hippocampus/metabolism/pathology MH - Humans MH - Male MH - Neurons/metabolism/pathology MH - Plaque, Amyloid/genetics/metabolism/pathology MH - Polymorphism, Genetic/*genetics MH - Synaptophysin/metabolism MH - Temporal Lobe/*metabolism/pathology EDAT- 2005/05/19 09:00 MHDA- 2005/07/16 09:00 CRDT- 2005/05/19 09:00 PHST- 2004/08/27 00:00 [received] PHST- 2004/12/24 00:00 [revised] PHST- 2005/01/19 00:00 [accepted] PHST- 2005/05/19 09:00 [pubmed] PHST- 2005/07/16 09:00 [medline] PHST- 2005/05/19 09:00 [entrez] AID - S0014-4886(05)00040-3 [pii] AID - 10.1016/j.expneurol.2005.01.026 [doi] PST - ppublish SO - Exp Neurol. 2005 Jul;194(1):91-6. doi: 10.1016/j.expneurol.2005.01.026.