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Gene Therapy Models of Alzheimer’s Disease and Other Dementias

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Gene Therapy for Neurological Disorders

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1382))

Abstract

Dementias are among the most common neurological disorders, and Alzheimer’s disease (AD) is the most common cause of dementia worldwide. AD remains a looming health crisis despite great efforts to learn the mechanisms surrounding the neuron dysfunction and neurodegeneration that accompanies AD primarily in the medial temporal lobe. In addition to AD, a group of diseases known as frontotemporal dementias (FTDs) are degenerative diseases involving atrophy and degeneration in the frontal and temporal lobe regions. Importantly, AD and a number of FTDs are collectively known as tauopathies due to the abundant accumulation of pathological tau inclusions in the brain. The precise role tau plays in disease pathogenesis remains an area of strong research focus. A critical component to effectively study any human disease is the availability of models that recapitulate key features of the disease. Accordingly, a number of animal models are currently being pursued to fill the current gaps in our knowledge of the causes of dementias and to develop effective therapeutics. Recent developments in gene therapy-based approaches, particularly in recombinant adeno-associated viruses (rAAVs), have provided new tools to study AD and other related neurodegenerative disorders. Additionally, gene therapy approaches have emerged as an intriguing possibility for treating these diseases in humans. This chapter explores the current state of rAAV models of AD and other dementias, discuss recent efforts to improve these models, and describe current and future possibilities in the use of rAAVs and other viruses in treatments of disease.

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Acknowledgements

This work was supported by NIH/NIA grant R01AG044372 (N.M.K.).

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Authors and Affiliations

  1. Department of Translational Science and Molecular Medicine, College of Human Medicine, Michigan State University, 333 Bostwick Avenue NE, Grand Rapids, MI, 49503, USA

    Benjamin Combs, Andrew Kneynsberg & Nicholas M. Kanaan Ph.D.

  2. Neuroscience Program, Michigan State University, Grand Rapids, MI, USA

    Andrew Kneynsberg & Nicholas M. Kanaan Ph.D.

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  1. Benjamin Combs
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  2. Andrew Kneynsberg
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Correspondence to Nicholas M. Kanaan Ph.D. .

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  1. Translational Science and Molecular Medicine, Michigan State University, College of Human Science, Grand Rapids, Michigan, USA

    Fredric P. Manfredsson

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Combs, B., Kneynsberg, A., Kanaan, N.M. (2016). Gene Therapy Models of Alzheimer’s Disease and Other Dementias. In: Manfredsson, F. (eds) Gene Therapy for Neurological Disorders. Methods in Molecular Biology, vol 1382. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3271-9_25

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