Alan Nagahara, Ph.D.
Associate Project Scientist

Current Research
We and others have demonstrated that Nerve Growth Factor (NGF) gene therapy can prevent cholinergic neuronal loss and augment cholinergic function in experimental animal models. Subsequently, these findings have led to ongoing clinical trials to examine NGF gene therapy in patients with Alzheimer’s disease to delay or even prevent degeneration of cholinergic neurons in the basal forebrain.

I am currently investigating another neurotrophic factor called Brain-derived neurotrophic factor (BDNF) as a potential therapeutic agent in reversing the cell loss and synaptic dysfunction in models of Alzheimer’s disease.

In the initial stages of Alzheimer’s disease, the entorhinal cortex exhibits neuropathology and cell loss that is thought to contribute to the early memory loss in AD patients. Therefore, our studies have examined whether BDNF delivery to the entorhinal cortex can reverse memory deficits and synaptic loss in animal models of AD. We have demonstrated that BDNF gene therapy in the entorhinal cortex of a transgenic mouse model of Alzheimer’s disease (overproduction of beta-amyloid) reverses memory impairments in two different tasks and reduces the loss of synaptic markers in the region. In addition, BDNF gene delivery reverses the loss of neurons in the entorhinal cortex following a lesion of the perforant pathway. We have also found that BDNF can prevent cell death of entorhinal cortical neurons from the neurotoxic effect of beta-amyloid in vitro. Current research is aimed at understanding the neuroprotective and memory-enhancing mechanisms of BDNF to develop a potential novel therapeutic approach for AD.


Recent Publications

Nagahara AH, Schroeder BE, Wang L, Blesch A, Rockenstein E, Chiba AA, Koo E, Masliah E and Tuszynski, MH. BDNF Gene Delivery Reverses Cognitive and Synaptic Alterations in APP Transgenic Mice Independent of Effects on Amyloid Plaque Load. (Submitted).

Nagahara AH and Tuszynski MH. Growth Factors and Alzheimer’s Disease. In S.S. Sisodia and R.E. Tanzi (Eds.), Alzheimer’s Disease: Advances in Genetics, Molecular and Cellular Biology. New York: Springer, 2006: pp. 257-277.

Nagahara A and Tuszynski MH. The ageless question: what accounts for age-related cognitive decline? Science: Aging Knowledge Environ (2004): 2(19):20.