Apparent Behavioral Benefits of Tau Overexpression in P301L Tau Transgenic Mice

Issue title: Animal Models of Alzheimer's Disease: Therapeutic Implications

Guest editors: Diana Woodruff-Pak

Article type: Research Article

Authors: Morgan, Dave^{a; *} | Munireddy, Sanjay^a | Alamed, Jennifer^a | DeLeon, Jason^a | Diamond, David M.^{b; e} | Bickford, Paula^{c; e} | Hutton, Michael^d | Lewis, Jada^d | McGowan, Eileen^d | Gordon, Marcia N.^a

Affiliations: [a] Alzheimer Research Laboratory, Department of Pharmacology, University of South Florida, Tampa, FL, USA | [b] Departments of Psychology, Molecular Pharmacology and Center for Preclinical and Clinical Research on PTSD, University of South Florida, Tampa, FL, USA | [c] Center of Excellence for Aging and Brain Repair and Department of Neurosurgery, University of South Florida, Tampa, FL, USA | [d] Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL, USA | [e] James A. Haley Veterans Administration Medical Center, Tampa, FL, USA

Correspondence: [*] Corresponding author: Dave Morgan, PhD, Alzheimer Research Laboratory, MDC Box 9, University of South Florida, Tampa, FL 33612-4799, USA. Tel.: +1 813 974 3949; Fax: +1 813 974 2565; E-mail: [email protected].

Abstract: Transgenic mice expressing human tau containing the P301L tau mutation (JNPL3; tau mice) develop motor neuron loss, paralysis and death between 7 and 12 months. Surprisingly, at 5 and 7 months of age, tau transgenic mice were superior to other genotypes in the rotarod task, and had near perfect scores on the balance beam and coat hanger tests. One tau transgenic mouse was performing at a superior level in the rotarod one day prior to developing paralysis. Cognitive function was also normal in the tau mice evaluated in the radial arm water maze and the Y-maze tasks. We also crossed the tau transgenic mice with Tg2576 amyloid-β protein precursor (AβPP) transgenic mice. Although AβPP mice were deficient in the radial arm maze task, AβPP + tau mice were not impaired, implying a benefit of the tau transgene. Some mice were homozygous for the retinal degeneration mutation (rd/rd) and excluded from the genotype analysis. Only the water maze task discriminated the rd/rd mice from nontransgenic mice. In conclusion, it seems that the modest tau overexpression or the presence of mutant tau in the JNPL3 tau mice may provide some benefit with respect to motor and cognitive performance before the onset of paralysis.

Keywords: Amyloid, rotarod, tau, transgenic mice, water maze, Y-maze

DOI: 10.3233/JAD-2008-15407

Journal: Journal of Alzheimer's Disease, vol. 15, no. 4, pp. 605-614, 2008