Chapter 13: A Non-transgenic Rat Model of Sporadic Alzheimer's Disease

Alzheimer's disease occurs both in familial and or sporadic forms. The familial AD accounts for less than 1% of the cases and is caused by specific mutations in amyloid precursor protein, presenilin 1 or presenilin 2 genes. The nature of the etiological factors for the sporadic form of AD, which accounts for over 99% of the cases, is at present not well understood. To date most of the animal models are transgenic mice which express the familial AD mutations alone or in combination with tau mutations of frontotemporal dementia. This chapter discusses the sparseness of animal models of sporadic AD and describes a novel adeno associated virus (AAV) vector-induced experimental rat model of this disease. This model replicates the overexpression of the C-terminal fragment of I2PP2A, I2CTF, in rat brain using the AAV vector. The AAV-I2CTF rats show intraneuronal accumulation of Ab1–42 and abnormally hyperphosphorylated tau but no Ab plaques or neurofibrillary tangles by nine months, studied so far, but are cognitively impaired in Morris water maze spatial reference memory task. As compared with generation of transgenic animals, the AAV-induced expression system is rapid, highly reproducible, and within the reach of most research laboratories as well as allows the expression of the desired gene in a spatial and temporal controlled manner.