Inbal Maniv, Mahasen Sarji, Anwar Bdarneh, Alona Feldman, Roi Ankawa, Elle Koren, Inbar Magid-Gold, Noa Reis, Despina Soteriou, Shiran Salomon-Zimri, Tali Lavy, Ellina Kesselman, Naama Koifman, Thimo Kurz, Oded Kleifeld, Daniel Michaelson, Fred W van Leeuwen, Bert M Verheijen, Yaron Fuchs, Michael H Glickman
Alzheimer's disease (AD) is characterized by toxic protein accumulation in the brain. Ubiquitination is essential for protein clearance in cells, making altered ubiquitin signaling crucial in AD development. A defective variant, ubiquitin B + 1 (UBB+1 ), created by a non-hereditary RNA frameshift mutation, is found in all AD patient brains post-mortem. We now detect UBB+1 in human brains during early AD stages. Our study employs a 3D neural culture platform derived from human neural progenitors, demonstrating that UBB+1 alone induces extracellular amyloid-β (Aβ) deposits and insoluble hyperphosphorylated tau aggregates...
September 22, 2023: Nature Communications