Decreased levels of BDNF protein in Alzheimer temporal cortex are independent of BDNF polymorphisms

Jung Lee, Hiroaki Fukumoto, Jennifer Orne, Jochen Klucken, Susan Raju, Charles R. Vanderburg, Michael C. Irizarry, Bradley T. Hyman*, Martin Ingelsson

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

96 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)91-96
Number of pages6
JournalExperimental Neurology
Volume194
Issue number1
DOIs
Publication statusPublished - Jul 2005
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Association studies
  • BDNF
  • ELISA
  • Gene polymorphisms
  • Synaptophysin

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