| First Author | Lord A | Year | 2011 |
| Journal | Am J Pathol | Volume | 178 |
| Issue | 5 | Pages | 2286-98 |
| PubMed ID | 21514441 | Mgi Jnum | J:171581 |
| Mgi Id | MGI:4950599 | Doi | 10.1016/j.ajpath.2011.01.052 |
| Citation | Lord A, et al. (2011) Observations in APP Bitransgenic Mice Suggest that Diffuse and Compact Plaques Form via Independent Processes in Alzheimer's Disease. Am J Pathol 178(5):2286-98 |
| abstractText | Studies of familial Alzheimer's disease suggest that misfolding and aggregation of amyloid-beta (Abeta) peptides initiate the pathogenesis. The Arctic mutation of Abeta precursor protein (APP) results in AD, and Arctic Abeta is more prone to form Abeta protofibrils and extracellular deposits. Herein is demonstrated that the burden of diffuse Abeta deposits but not compact plaques is increased when tg-Swe mice are crossed with tg-ArcSwe mice synthesizing low levels of Arctic Abeta. The diffuse deposits in bitransgenic mice, which contain primarily wild-type Abeta42, accumulate in regions both with and without transgene expression. However, APP processing, when compared with tg-Swe, remains unchanged in young bitransgenic mice, whereas wild-type Abeta42 aggregation is accelerated and fibril architecture is altered in vitro and in vivo when a low level of Arctic Abeta42 is introduced. Thus, the increased number of diffuse deposits is likely due to physical interactions between Arctic Abeta and wild-type Abeta42. The selective increase of a single type of parenchymal Abeta deposit suggests that different pathways lead to formation of diffuse and compact plaques. These findings could have general implications for Alzheimer's disease pathogenesis and particular relevance to patients heterozygous for the Arctic APP mutation. Moreover, it further illustrates how Abeta neuropathologic features can be manipulated in vivo by mechanisms similar to those originally conceptualized in prion research. |
