Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer's disease.

TitleNeuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer's disease.
Publication TypeJournal Article
Year of Publication2009
AuthorsNagahara, AH, Merrill DA, Coppola G, Tsukada S, Schroeder BE, Shaked GM, Wang L, Blesch A, Kim A, Conner JM, Rockenstein E, Chao MV, Koo EH, Geschwind D, Masliah E, Chiba AA, Tuszynski MH
JournalNature medicine
Volume15
Issue3
Pagination331-7
Date Published2009 Mar
ISSN1546-170X
KeywordsAlzheimer Disease, Animals, Brain-Derived Neurotrophic Factor, Disease Models, Animal, Mice, Mice, Transgenic, Neuroprotective Agents, Primates
Abstract

Profound neuronal dysfunction in the entorhinal cortex contributes to early loss of short-term memory in Alzheimer's disease. Here we show broad neuroprotective effects of entorhinal brain-derived neurotrophic factor (BDNF) administration in several animal models of Alzheimer's disease, with extension of therapeutic benefits into the degenerating hippocampus. In amyloid-transgenic mice, BDNF gene delivery, when administered after disease onset, reverses synapse loss, partially normalizes aberrant gene expression, improves cell signaling and restores learning and memory. These outcomes occur independently of effects on amyloid plaque load. In aged rats, BDNF infusion reverses cognitive decline, improves age-related perturbations in gene expression and restores cell signaling. In adult rats and primates, BDNF prevents lesion-induced death of entorhinal cortical neurons. In aged primates, BDNF reverses neuronal atrophy and ameliorates age-related cognitive impairment. Collectively, these findings indicate that BDNF exerts substantial protective effects on crucial neuronal circuitry involved in Alzheimer's disease, acting through amyloid-independent mechanisms. BDNF therapeutic delivery merits exploration as a potential therapy for Alzheimer's disease.

DOI10.3928/01913913-20090706-05
Alternate JournalNat. Med.