ABSTRACT
Transgenic approaches to modeling AD began in 1991 with the discovery of the first pathogenic mutations in APP (Goate et al., 1991). Early attempts to model the disease were considered by many to have failed as none showed the pathognomic features of the disease, which include beta amyloid (Aβ) containing plaques and tau containing tangles. Since 1995, transgenic modeling has regained credibility following the publication of the PDAPP mouse in 1995 (Games et al., 1995) and the Tg2576 mouse in 1996 (Hsaio et al., 1996). Both these mice display Aβ containing deposits in regions of the brain affected by AD. The success of these mice is almost certainly related to the very high levels of Aβ generated through the use of cleverly designed transgenes as it appears that elevation of Aβ levels above a critical concentration will initiate the fibrillarization process which leads to extracellular deposition of both Aβ1-42 and Aβ1-4. Although these mice are excellent model systems in which to study Aβ elevation and deposition, they are not complete models of Alzheimer’s disease as neither show tau containing tangles or overt neuronal loss.
