Natural Non-Transgenic Animal Models for Research in Alzheimer’s Disease
Pp. 255-274 (20)
The most common animal models currently used for Alzheimer disease (AD)
research are transgenic mice that express a mutant form of human Aβ precursor protein
(APP) and/or some of the enzymes implicated in their metabolic processing. However,
these transgenic mice carry their own APP and APP-processing enzymes, which may
interfere in the production of different amyloid-beta (Aβ) peptides encoded by the
human transgenes. Additionally, the genetic backgrounds of the different transgenic
mice are a possible confounding factor with regard to crucial aspects of AD that they
may (or may not) reproduce. Thus, although the usefulness of transgenic mice is
undisputed, we hypothesized that additional relevant information on the
physiopathology of AD could be obtained from other natural non-transgenic models.
We have analyzed the chick embryo and the dog, which may be better experimental
models because their enzymatic machinery for processing APP is almost identical to
that of humans. The chick embryo is extremely easy to access and manipulate. It could
be an advantageous natural model in which to study the cell biology and developmental
function of APP and a potential assay system for drugs that regulate APP processing.
The dog suffers from an age-related syndrome of cognitive dysfunction that naturally
reproduces key aspects of AD including Aβ cortical pathology, neuronal degeneration
and learning and memory disabilities. However, dense core neuritic plaques and
neurofibrillary tangles have not been consistently demonstrated in the dog. Thus, these
species may be natural models with which to study the biology of AD, and could also
serve as assay systems for Aβ-targeted drugs or new therapeutic strategies against this
Aβ, APP, Chick embryo, dog, dolphin, rabbit, rat.