Chapter 5.5 Transgenic mouse models of Alzheimer's disease and episodic-like memory

In this chapter, we discuss examples of behavioral studies of several transgenic models of Alzheimer's-type amyloidosis, providing examples of approaches and comparisons of outcomes for reference, episodic-like, and working memory. Most studies have attempted to link changes in the levels of Aβ peptides (the primary component of senile plaques in Alzheimer's disease) to the onset of deficits in one type of memory, focusing on one behavioral task to assess specific cognitive functions. Studies that have analyzed concurrent changes in different memory systems have shown that tasks requiring flexible use of information "what," "where," and/or "when" (the episodic-like memory tasks) are useful in detecting losses in memory function. In general, impairments in episodic-like memory were detected earlier than in reference memory and were highly correlated with amyloid plaque load. An analysis of the literature, including our own studies, indicates that the accumulation of Aβ peptides impacts the cognitive functions of mice differentially as a function of age and Aβ amyloid load. Cognitive decline appears to be gradually progressive with parallels to human patients in that episodic-like memory is the first memory system affected. More importantly, the physical form of Aβ peptide (monomer, soluble oligomer, or fibril) that mediates memory deficits may differ at various stages of the disease, a finding that could alter strategies for treatment for this disease.