Alzheimer's mice: Groping in the darkness

Alzheimer's mice: Groping in the darkness

The recent publication of what is at least the tenth transgenic mouse model of Alzheimer's disease has rekindled the debate over which model most accurately reflects the progression and symptoms of the disease.

Several transgenic mouse models have been made by companies and academic labs, each with different advantages and disadvantages for the study of Alzheimer's disease (AD). However, trying to create a model of a disease that is not well understood even in humans in an organism with non-human physiology is difficult at best, and no model produced so far comprehensively reflects the pathological and behavioral features of AD.

This means that companies trying to develop therapeutics have had to choose a model to use without a detailed understanding of the disease and without benefit of an academic consensus over which AD mouse best reflects the human condition.

Existing mouse models can be divided into three categories: transgenics that overexpress full-length APP and form plaques thought to be authentic; C100 transgenics that cause neuronal death (another hallmark of AD) but may simply be toxic; and "humanized" mice that model human physiology and genetics without necessarily causing disease symptoms.

The key split among researchers is between the full-length APP transgenics that display normal processing, plaque formation, and sometimes memory problems but no AD-like neuronal death and the C100 transgenics that show neuronal death and memory

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