| First Author | Capsoni S | Year | 2013 |
| Journal | J Alzheimers Dis | Volume | 33 |
| Issue | 2 | Pages | 357-71 |
| PubMed ID | 22986780 | Mgi Jnum | J:210074 |
| Mgi Id | MGI:5569468 | Doi | 10.3233/JAD-2012-121399 |
| Citation | Capsoni S, et al. (2013) SorLA deficiency dissects amyloid pathology from tau and cholinergic neurodegeneration in a mouse model of Alzheimer's disease. J Alzheimers Dis 33(2):357-71 |
| abstractText | Sortilin-related receptor with A-type repeats (SorLA, also known as LR11) has been implicated in Alzheimer's disease (AD). Thus, genetic studies associated SorLA gene variants with the risk of sporadic AD. Also, in vitro and in vivo studies showed that SorLA impairs processing of the amyloid-beta protein precursor (AbetaPP) to amyloid-beta. In particular, it has been found that loss of SorLA accelerates senile plaque deposition in mouse models overexpressing mutant forms of human AbetaPP and presenilin 1. Here we tested the possibility that SorLA deficiency also interferes with behavioral and neuropathological endpoints in an alternative murine AD model, the AD10 anti-nerve growth factor (NGF) mouse, in which amyloid-beta accumulation derives from the altered processing of endogenous AbetaPP. In addition to alterations in AbetaPP processing, AD10 mice also show cholinergic deficit and tau hyperphosphorylation resulting in behavioral deficits in learning and memory paradigms. We found that the loss of SorLA not only exacerbates early amyloid pathology but, at the same time, protects from cholinergic deficit and from early phospho-tau mislocalization. The results show that in the AD10 anti-NGF mouse model the AbetaPP processing-related aspects of neurodegeneration can be dissociated from those related to tau posttranslational processing and to cholinergic phenotypic maintenance by modulation of SorLA expression. We suggest that SorLA regulates different aspects of neurodegeneration in a complex way, supporting the hypothesis that SorLA expression might be critical not only for amyloid-related pathology but also for other cellular processes altered in AD. |
