Alzheimer disease (AD), the most common
cause of dementia, accounts for approximately
two-thirds of all dementia cases and
afflicts more than 35 million individuals worldwide,
including more than 5.4 million Americans.
It is a relentlessly progressive disorder
that typically manifests initially by severe loss
of memory, particularly of episodic memory.
At present, the disorder is not curable, thereby
increasing the urgency of developing and characterizing
relevant animal models to facilitate
translational research and preclinical drug
development.
Research progress over the past two decades,
including the elucidation of AD susceptibility
and causative genes as well as other proteins
involved in the pathogenic process, has profoundly
facilitated the development of genetically
altered mouse models (see http://www.
alzforum.org/res/com/tra for a listing of currently
available models). Animal models have
played a major role in defining critical disease-
related mechanisms and have been at the
forefront of evaluating novel therapeutic approaches,
with many treatments currently in
clinical trial owing their origins to studies initially
performed in mice. Nevertheless, there
are significant translational issues that have
been raised of late, as there has been some
potential discordance between preclinical drug
studies and human clinical trials.