| First Author | He Z | Year | 2018 |
| Journal | Nat Med | Volume | 24 |
| Issue | 1 | Pages | 29-38 |
| PubMed ID | 29200205 | Mgi Jnum | J:311456 |
| Mgi Id | MGI:6766491 | Doi | 10.1038/nm.4443 |
| Citation | He Z, et al. (2018) Amyloid-beta plaques enhance Alzheimer's brain tau-seeded pathologies by facilitating neuritic plaque tau aggregation. Nat Med 24(1):29-38 |
| abstractText | Alzheimer's disease (AD) is characterized by extracellular amyloid-beta (Abeta) plaques and intracellular tau inclusions. However, the exact mechanistic link between these two AD lesions remains enigmatic. Through injection of human AD-brain-derived pathological tau (AD-tau) into Abeta plaque-bearing mouse models that do not overexpress tau, we recapitulated the formation of three major types of AD-relevant tau pathologies: tau aggregates in dystrophic neurites surrounding Abeta plaques (NP tau), AD-like neurofibrillary tangles (NFTs) and neuropil threads (NTs). These distinct tau pathologies have different temporal onsets and functional consequences on neural activity and behavior. Notably, we found that Abeta plaques created a unique environment that facilitated the rapid amplification of proteopathic AD-tau seeds into large tau aggregates, initially appearing as NP tau, which was followed by the formation and spread of NFTs and NTs, likely through secondary seeding events. Our study provides insights into a new multistep mechanism underlying Abeta plaque-associated tau pathogenesis. |
