28 February 2009

Possible new treatment for Alzheimer’s

Protein targets Alzheimer's-like ailments: a possible future treatment for Alzheimer’s disease
Dementia News (Alzheimer’s Australia): 21 February 2008
A group of researchers from the University of California and the New York University School of Medicine have been investigating a novel approach to the treatment of brain impairment, including that associated with Alzheimer’s disease. Before discussing their work it might be helpful to spend a moment on a brief orientation to the three main objects of interest — brain-derived neurotrophic factor, the hippocampus, and the entorhinal cortex.

Brain-derived neurotrophic factor (BDNF) is a protein that helps brain cells to survive and encourages the growth and specialisation of new brain cells and synapses (spaces between brain cells across which chemical messages travel). In the brain, BDNF is active in a number of regions, including the hippocampus, which is an area of the brain that is affected in Alzheimer’s disease. The hippocampus has its strongest connections with an area of the brain next to it called the entorhinal cortex. The entorhinal cortex is involved in memory consolidation and memory optimisation in sleep. It also contains a map of the spatial environment, allowing individuals to orient themselves in the space around them and to manage direction. The entorhinal cortex is another area affected in Alzheimer’s disease.

The researchers set out to examine whether administering BNDF to the brains of non-human animals with Alzheimer’s-like disease would have therapeutic benefits. They began with amyloid-transgenic mice, that is, mice who had been genetically modified to develop an Alzheimer’s-like disease. After disease onset, the researchers administered BNDF to the mice. There were a number of outcomes. Synapse loss was reversed; incorrect gene expression was partially normalised; there was improvement in cell signalling; and learning and memory functions were restored. The researchers turned to aged rats, whose brains they infused with BDNF. The rats showed a reversal in cognitive decline; improvement in gene expression that had been affected by age; and restoration in cell signalling.

The researchers also examined the effects of BNDF on the brain cells in the entorhinal cortex in adult rats and primates. They reported that in those individuals who had lesions in their brains that would cause brain cell death in the entorhinal cortex, BDNF prevented it. And in aged primates, BDNF reversed brain-cell-shrinkage and went some way to improving age-related cognitive impairment. On the basis of these findings, the researchers write that it would be of value to explore the potential of BDNF as a possible therapy for Alzheimer’s disease.

There will need to be considerably more research before BNDF can be trialled in humans. At present the only method of delivery is by direct injection into the brain.

Study reference:
Nagahara AH; Merrill DA; Giovanni Coppola G; et al. 2009. Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer's disease. Nature Medicine. doi:10.1038/nm.1912

Also see Alzheimer’s News posting “Animal study paves way for novel approach to treating Alzheimer’s” (15 February 2009).

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