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Comment & Response
May 2014

Serum Brain-Derived Neurotrophic Factor as a Predictor of Incident Dementia—Reply

Author Affiliations
  • 1Department of Neurology, Boston University School of Medicine, Boston, Massachusetts
  • 2The Framingham Heart Study, Boston University School of Medicine, Boston, Massachusetts
JAMA Neurol. 2014;71(5):653-654. doi:10.1001/jamaneurol.2014.215

In Reply We thank Dr Hashimoto for highlighting the presence and opposing actions of 2 circulating proteolytic isoforms of brain-derived neurotrophic factor (BDNF), proBDNF, and mature BDNF. In the context of Alzheimer disease (AD), mature BDNF, acting through the TrkB receptor, promotes cell survival and dendritic spine formation while proBDNF induces apoptosis and dendritic spine pruning in the hippocampus.1 In animal models of learning and memory formation, the conversion of proBDNF to mature BDNF is necessary for synaptic long-term potentiation in glutamergic synapses and the acquisition and consolidation of memories, whereas elevated levels of proBDNF mediate synaptic long-term depression and memory extinction.1 Hence, mature BDNF rather than proBDNF appears more likely to reduce the risk for AD. However, in postmortem studies of human brains, both proBDNF and mature BDNF levels were reduced in the cortex of persons with mild cognitive impairment2 and AD.2,3 We have previously shown in the Framingham Study cohort that TrkB levels were increased in the hippocampus of cognitively normal persons with early AD pathology compared with cognitively normal control individuals with no AD pathology; this may represent a compensatory response to the decline in BDNF levels and a biological basis for cognitive reserve.4

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