Genetic Models of Alzheimer’s Disease: The Influence of Apolipoprotein E allele Isoforms on Behaviour in Laboratory Animals

Abstract

Alzheimer's disease (AD) is a neuro degenerative disorder that initially presents as a neurocognitive impairment focused on impaired episodic memory. The clinical course and severity of the cognitive symptoms of AD follows the observed postmortem pathology of the disease and generally occurs in distinct stages (Braak and Braak 1991; Thai et al. 2006). The initial impairment in episodic memory has been associated with neuropathology originating within the hippocampus and the entorhinal cortex. AD brain pathology then typically radiates from the hippocampus and entorhinal cortex to association cortices and subcortical structures (including the amygdala and nucleus basalis of Meynert) leading to a gradual erosion of other cognitive domains (including executive functioning, speed of perceptuo-motor processing and visuospatial skills; Arnold et al. 1991). In this chapter, we will first discuss the major pathological characteristics of AD, including beta amyloid plaques and neurofibrillary tangles. In the next section of this chapter, we will discuss genetic factors which are relevant in AD, with a specific focus on variants of the apolipoprotein E gene and how these polymorphisms influence the pathophysiological mechanisms that have been previously outlined. Once these topics have been introduced, the last section of this chapter will detail current research that has used apolipoprotein E genetic mouse models to investigate cognitive outcomes that are relevant for AD. This last section of the chapter will focus on behavioural models that target episodic memory function as—in a clinical context—this is the cognitive capacity of primary interest in the early stages of 'conversion' from healthy ageing to AD. (PsycINFO Database Record (c) 2019 APA, all rights reserved)