Citations 2
Current directions in tau research: Highlights from Tau 2020
Sexton, Claire E. , Snyder, Heather M. , Boxer, Adam L. , Brannelly, Patrick , Brion, Jean‐Pierre , Buée, Luc , Cacace, Angela , Chételat, Gaël , Citron, Martin , DeVos, Sarah L. , Diaz, Kristophe , Feldman, Howard , Frost, Bess , Goate, Alison , Gold, Michael , Johnson, Keith A. , Kerwin, Diana , Mummery, Catherine J. , Mutamba, James, Quiroz, Yakeel T. , Rabinovici, Gil D. , Rommel, Amy, Shulman, Melanie , Toledo‐Sherman, Leticia , Weninger, Stacie, Wildsmith, Kristin R., Worley, Susan, Carrillo, María C. , Sexton, Claire , Patterson, Marc C. , Rabinovici, Gil D , Feldman, Howard H , Goate, Alison M , Beher, Dirk , Hyman, Bradley T. , Karch, Celeste M. , Koroshetz, Walter J. , Litvan, Irene , Morris, Huw R.
Alzheimer's & Dementia | September 28, 2021 | Volume: 18 | Issue: 5 | Pages: 988-1007
AbstractStudies supporting a strong association between tau deposition and neuronal loss, neurodegeneration, and cognitive decline have heightened the allure of tau and tau‐related mechanisms as therapeutic targets. In February 2020, leading tau experts from around the world convened for the first‐ever Tau2020 Global Conference in Washington, DC, co‐organized and cosponsored by the Rainwater Charitable Foundation, the Alzheimer's Association, and CurePSP. Representing academia, industry, government, and the philanthropic sector, presenters and attendees discussed recent advances and current directions in tau research. The meeting provided a unique opportunity to move tau research forward by fostering global partnerships among academia, industry, and other stakeholders and by providing support for new drug discovery programs, groundbreaking research, and emerging tau researchers. The meeting also provided an opportunity for experts to present critical research‐advancing tools and insights that are now rapidly accelerating the pace of tau research.
Involvement of β-site APP cleaving enzyme 1 (BACE1) in amyloid precursor protein-mediated enhancement of memory and activity-dependent synaptic plasticity
Ma, Huifang, Lesné, Sylvain , Kotilinek, Linda, Steidl‐Nichols, Jill, Sherman, Mathew A. , Younkin, Linda H., Younkin, Steven G. , Forster, Colleen L. , Sergeant, Nicolas , Delacourte, André, Vassar, Robert , Citron, Martin , Kofuji, Paulo , Boland, Linda M. , Ashe, Karen H.
Proceedings of the National Academy of Sciences | April 30, 2007 | Volume: 104 | Issue: 19 | Pages: 8167-8172
The amyloid precursor protein (APP) undergoes sequential cleavages to generate various polypeptides, including the amyloid-β protein (Aβ), which forms amyloid plaques in Alzheimer's disease (AD), secreted APPα (sAPPα) which enhances memory, and the APP intracellular domain (AICD), which has been implicated in the regulation of gene transcription and calcium signaling. The β-site APP cleaving enzyme 1 (BACE1) cleaves APP in an activity-dependent manner to form Aβ, AICD, and secreted APPβ. Because this neural activity was shown to diminish synaptic transmission in vitro [Kamenetz F, Tomita T, Hsieh H, Seabrook G, Borchelt D, Iwatsubo T, Sisodia S, Malinow R (2003) Neuron 37:925–937], the prevailing notion has been that this pathway diminishes synaptic function. Here we investigated the role of this pathway in vivo . We studied transgenic mice overproducing APP that do not develop AD pathology or memory deficits but instead exhibit enhanced spatial memory. We showed enhanced synaptic plasticity in the hippocampus that depends on prior synaptic activity. We found that the enhanced memory and synaptic plasticity are abolished by the ablation of one or both copies of the BACE1 gene, leading to a significant decrease in AICD but not of any other APP cleavage products. In contrast to the previously described negative effect of BACE1-mediated cleavage of APP on synaptic function in vitro , our in vivo work indicates that BACE1-mediated cleavage of APP can facilitate learning, memory, and synaptic plasticity.