PLD3 affects axonal spheroids and network defects in Alzheimer’s disease

• Published in: Nature (London) Vol. 612; no. 7939; pp. 328 - 337
• Main Authors: Yuan, Peng, Zhang, Mengyang, Tong, Lei, Morse, Thomas M., McDougal, Robert A., Ding, Hui, Chan, Diane, Cai, Yifei, Grutzendler, Jaime
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08.12.2022; Nature Publishing Group
• Subjects: 13/1; 13/44; 13/51; 14/19; 14/28; 14/34; 14/35; 14/63; 14/69; 42/41; 631/378/1689/1283; 631/378/3920; 631/378/87; 64/60; Abnormalities; Accumulation; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Amyloid; Animals; Axon guidance; Axons - metabolism; Axons - pathology; Biosynthesis; Calcium channels (voltage-gated); Calcium imaging; Circuits; Cognitive ability; Disease Models, Animal; Disruption; Electric currents; Electrical conduction; Humanities and Social Sciences; Mice; multidisciplinary; Neural networks; Neurodegenerative diseases; Phospholipase D - metabolism; Propagation; Science; Science (multidisciplinary); Signal to noise ratio; Spheroids; Spheroids, Cellular - metabolism

The precise mechanisms that lead to cognitive decline in Alzheimer’s disease are unknown. Here we identify amyloid-plaque-associated axonal spheroids as prominent contributors to neural network dysfunction. Using intravital calcium and voltage imaging, we show that a mouse model of Alzheimer’s disea...