Gene Therapy Models of Alzheimer’s Disease and Other Dementias

  • Benjamin Combs
  • Andrew Kneynsberg
  • Nicholas M. Kanaan
Part of the Methods in Molecular Biology book series (MIMB, volume 1382)


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.

Key words

Tau protein Neurofibrillary tangle Recombinant adeno-associated virus Hippocampus Entorhinal cortex Animal model 



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


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Benjamin Combs
    • 1
  • Andrew Kneynsberg
    • 1
    • 2
  • Nicholas M. Kanaan
    • 1
    • 2
  1. 1.Department of Translational Science and Molecular Medicine, College of Human MedicineMichigan State UniversityGrand RapidsUSA
  2. 2.Neuroscience ProgramMichigan State UniversityGrand RapidsUSA

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