Alzheimer's disease (AD), the most common cause of dementia among the elderly, may either represent the far end of a continuum that begins with age-related memory decline or a distinct pathobiological process. Although mice that faithfully model all aspects of AD do not yet exist, current mouse models have provided valuable insights into specific aspects of AD pathogenesis. We will argue that transgenic mice expressing amyloid precursor protein should be considered models of accelerated brain aging or asymptomatic AD, and the results of interventional studies in these mice should be considered in the context of primary prevention. Studies in mice have pointed to the roles of soluble beta-amyloid (Aβ) oligomers and soluble tau in disease pathogenesis and support a model in which soluble Aβ oligomers trigger synaptic dysfunction, but formation of abnormal tau species leads to neuron death and cognitive decline severe enough to warrant a dementia diagnosis.
Bibliographical noteFunding Information:
This work was funded by grants from the National Institute for Neurological Disorders and Stroke, the National Institute on Aging, the National Institute for Mental Health, and gifts from B. Grossman and E.W. and A.M Tulloch.