title: Gene Therapy Models of Alzheimer's Disease and Other Dementias.
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.
authors.affiliation: Department of Translational Science and Molecular Medicine, College of Human Medicine, Michigan State University, 333 Bostwick Avenue NE, Grand Rapids, MI, 49503, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Combs
authors.affiliation: Department of Translational Science and Molecular Medicine, College of Human Medicine, Michigan State University, 333 Bostwick Avenue NE, Grand Rapids, MI, 49503, USA.|Neuroscience Program, Michigan State University, Grand Rapids, MI, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Kneynsberg
authors.affiliation: Department of Translational Science and Molecular Medicine, College of Human Medicine, Michigan State University, 333 Bostwick Avenue NE, Grand Rapids, MI, 49503, USA. Nicholas.kanaan@hc.msu.edu.|Neuroscience Program, Michigan State University, Grand Rapids, MI, USA. Nicholas.kanaan@hc.msu.edu.
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Kanaan
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology* / Q000628:therapy; D000818:Animals; D000229:Dependovirus / Q000235:genetics; D004195:Disease Models, Animal; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D051381:Rats; D024801:Tauopathies / Q000473:pathology* / Q000628:therapy; D016875:tau Proteins / Q000235:genetics
chemical_list: D016875:tau Proteins
keywords: Animal model; Entorhinal cortex; Hippocampus; Neurofibrillary tangle; Recombinant adeno-associated virus; Tau protein