Alzheimer Disease: An Update on Pathobiology and Treatment Strategies.

1. Cell. 2019 Oct 3;179(2):312-339. doi: 10.1016/j.cell.2019.09.001. Epub 2019 Sep 26. Alzheimer Disease: An Update on Pathobiology and Treatment Strategies. Long JM(1), Holtzman DM(2). Author information: (1)Department of Neurology, Hope Center for Neurological Disorders, Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110, USA. (2)Department of Neurology, Hope Center for Neurological Disorders, Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: holtzman@wustl.edu. Alzheimer disease (AD) is a heterogeneous disease with a complex pathobiology. The presence of extracellular β-amyloid deposition as neuritic plaques and intracellular accumulation of hyperphosphorylated tau as neurofibrillary tangles remains the primary neuropathologic criteria for AD diagnosis. However, a number of recent fundamental discoveries highlight important pathological roles for other critical cellular and molecular processes. Despite this, no disease-modifying treatment currently exists, and numerous phase 3 clinical trials have failed to demonstrate benefits. Here, we review recent advances in our understanding of AD pathobiology and discuss current treatment strategies, highlighting recent clinical trials and opportunities for developing future disease-modifying therapies. Copyright © 2019 Elsevier Inc. All rights reserved. DOI: 10.1016/j.cell.2019.09.001 PMCID: PMC6778042 PMID: 31564456 [Indexed for MEDLINE] Conflict of interest statement: DECLARATIONS OF INTEREST: J.M.L. reports serving as sub-investigator on the Lilly TRAILBLAZER trial but receives no financial compensation. D.M.H. reports being a cofounder of C2N Diagnostics, LLC; being on the scientific advisory board of C2N Diagnostics, Denali, and Genentech; and being a consultant for AbbVie and Idorsia. D.M.H is an inventor on a submitted patent #PCT/US2013/049333 “Antibodies to tau” that is licensed by Washington University to C2N Diagnostics. This patent was subsequently licensed to AbbVie.D.M.H. is an inventor on patent number 8,591,894 “Humanized antibodies that sequester amyloid beta” that was licensed by Washington University to Eli Lilly. D.M.H. is an inventor on patent number 8,232,107 “Methods for measuring the metabolism of neurally derived biomolecules in vivo” that was licensed by Washington University to C2N Diagnostics, LLC.