TY - JOUR
T1 - Decreased levels of BDNF protein in Alzheimer temporal cortex are independent of BDNF polymorphisms
AU - Lee, Jung
AU - Fukumoto, Hiroaki
AU - Orne, Jennifer
AU - Klucken, Jochen
AU - Raju, Susan
AU - Vanderburg, Charles R.
AU - Irizarry, Michael C.
AU - Hyman, Bradley T.
AU - Ingelsson, Martin
N1 - Funding Information:
This work was supported by NIH (AG 05134), The Swedish Brain Foundation, The Swedish Research Council, and the AFAR Beeson Award. We are also grateful to Harvard Center for Neurodegeneration and Repair (Harvard Medical School, Boston MA).
PY - 2005/7
Y1 - 2005/7
N2 - 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 APOEε4 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.
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 APOEε4 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.
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U2 - 10.1016/j.expneurol.2005.01.026
DO - 10.1016/j.expneurol.2005.01.026
M3 - Article
C2 - 15899246
AN - SCOPUS:19344373708
SN - 0014-4886
VL - 194
SP - 91
EP - 96
JO - Experimental Neurology
JF - Experimental Neurology
IS - 1
ER -