Neurofibrillary tangles are a prominent feature of AD pathology that are formed by aggregates of hyperphosphorylated Tau protein. Transgenic mouse lines that express human Tau mutations develop tangles and show deficits in mouse behavioral tests that model cognitive decline in AD. Evidence suggests that the majority of hippocampal- and entorhinal-based cognitive deficits (>80%) in AD patients is correlated with NFTs (Giannakopoulos et al., 2003); thus, evaluating Tau-dependent neural and behavioral deficits has strong translational value. As noted above (Fig. 2), NFT pathology is expressed in AD in a brain region-dependent manner originating in the entorhinal cortex and progressing to the hippocampus, other areas of the cortex, and limbic structures. Mouse lines that express mutations of human Tau (e.g., 3xTg-AD mice) also show this anatomical progression of pathology and are, therefore, useful for evaluating the impact of alcohol and other potential modifiable risk factors on the development of AD-like pathology.
