| First Author | Frost JL | Year | 2013 |
| Journal | Am J Pathol | Volume | 183 |
| Issue | 2 | Pages | 369-81 |
| PubMed ID | 23747948 | Mgi Jnum | J:199082 |
| Mgi Id | MGI:5500828 | Doi | 10.1016/j.ajpath.2013.05.005 |
| Citation | Frost JL, et al. (2013) Pyroglutamate-3 Amyloid-beta Deposition in the Brains of Humans, Non-Human Primates, Canines, and Alzheimer Disease-Like Transgenic Mouse Models. Am J Pathol 183(2):369-81 |
| abstractText | Amyloid-beta (Abeta) peptides, starting with pyroglutamate at the third residue (pyroGlu-3 Abeta), are a major species deposited in the brain of Alzheimer disease (AD) patients. Recent studies suggest that this isoform shows higher toxicity and amyloidogenecity when compared to full-length Abeta peptides. Here, we report the first comprehensive and comparative IHC evaluation of pyroGlu-3 Abeta deposition in humans and animal models. PyroGlu-3 Abeta immunoreactivity (IR) is abundant in plaques and cerebral amyloid angiopathy of AD and Down syndrome patients, colocalizing with general Abeta IR. PyroGlu-3 Abeta is further present in two nontransgenic mammalian models of cerebral amyloidosis, Caribbean vervets, and beagle canines. In addition, pyroGlu-3 Abeta deposition was analyzed in 12 different AD-like transgenic mouse models. In contrast to humans, all transgenic models showed general Abeta deposition preceding pyroGlu-3 Abeta deposition. The findings varied greatly among the mouse models concerning age of onset and cortical brain region. In summary, pyroGlu-3 Abeta is a major species of beta-amyloid deposited early in diffuse and focal plaques and cerebral amyloid angiopathy in humans and nonhuman primates, whereas it is deposited later in a subset of focal and vascular amyloid in AD-like transgenic mouse models. Given the proposed decisive role of pyroGlu-3 Abeta peptides for the development of human AD pathology, this study provides insights into the usage of animal models in AD studies. |
