| First Author | Nilsson P | Year | 2013 |
| Journal | Cell Rep | Volume | 5 |
| Issue | 1 | Pages | 61-9 |
| PubMed ID | 24095740 | Mgi Jnum | J:203777 |
| Mgi Id | MGI:5528736 | Doi | 10.1016/j.celrep.2013.08.042 |
| Citation | Nilsson P, et al. (2013) Abeta secretion and plaque formation depend on autophagy. Cell Rep 5(1):61-9 |
| abstractText | Alzheimer's disease (AD) is a neurodegenerative disease biochemically characterized by aberrant protein aggregation, including amyloid beta (Abeta) peptide accumulation. Protein aggregates in the cell are cleared by autophagy, a mechanism impaired in AD. To investigate the role of autophagy in Abeta pathology in vivo, we crossed amyloid precursor protein (APP) transgenic mice with mice lacking autophagy in excitatory forebrain neurons obtained by conditional knockout of autophagy-related protein 7. Remarkably, autophagy deficiency drastically reduced extracellular Abeta plaque burden. This reduction of Abeta plaque load was due to inhibition of Abeta secretion, which led to aberrant intraneuronal Abeta accumulation in the perinuclear region. Moreover, autophagy-deficiency-induced neurodegeneration was exacerbated by amyloidosis, which together severely impaired memory. Our results establish a function for autophagy in Abeta metabolism: autophagy influences secretion of Abeta to the extracellular space and thereby directly affects Abeta plaque formation, a pathological hallmark of AD. |
