P1–005: RAAV vectors to rapidly modify and model AD pathology in mice, rats, and guinea pigs
Year: 2006
Type: article
Abstract: It is generally acknowledged that our mouse models of AD only model particular pathologies. For example APP mice are superb models of Aβ deposition as amyloid, but do not develop overt tau pathology or neuronal loss. Thus, it is clear that in order to better understand the entire pathological cascade that results in AD we need better animal models. To develop novel models of Alzheimer's disease and more rapidly evaluate potential modifiers of amyloid deposition in APP mice. Several rAAV serotypes are used to directly transfer genes to the CNS of non–transgenic mice, APP mice, rats and guinea pigs. Delivery of rAAV encoding proteins that may modify AD pathology (e.g, anti–Aβ single chain antibodies, NADPH oxidase subunits, and RTN3) to neonatal APP mice enables one to examine effects on Aβ production and deposition in 3–6 months of time. Delivery of factors (e.g., proNGF) implicated in neuronal death enables us to rapidly extend in vitro results to the in vivo setting. Finally, ability to transduce the CNS of mice and guinea pigs enables us to determine whether other species may develop more robust AD–like pathology following delivery of transgenes that express Aβ. Using rAAV gene delivery it is feasible to achieve long–lasting high level transgen expression in the CNS of mice, rats and guinea pigs. Delivery of genes that are designed to alter Aβ dep[soption can be shown to do so in very short time periods with small group sizes. Moreover, other factors implicated in the pathological cascade of AD can be expressed and their effects on AD–like pathology evaluated. rAAV gene delivery complements current transgenic technologies used to develop novel AD models and modulate pathology in current models.
Source: Alzheimer s & Dementia
Institutions: Mayo Clinic, Mayo Clinic in Florida
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2746055087