Alzheimer disease causes the gradual deterioration of cognitive function, including severe memory loss and impairments in abstraction and reasoning. Understanding the complex changes that occur in the brain as the disease progresses—including the accumulation of amyloid plaques and neurofibrillary tangles—is critical for the development of successful therapeutic approaches.
Written and edited by leading experts in the field, this volume includes contributions covering all aspects of Alzheimer disease, from our current molecular understanding to therapeutic agents that could be used to treat and, ultimately, prevent it. Contributors discuss the biochemistry and cell biology of amyloid ß-protein precursor (APP), tau, presenilin, ß-secretase, and apolipoprotein E and their involvement in Alzheimer disease. They also review the clinical, neuropathological, imaging, and biomarker phenotypes of the disease; genetic alterations associated with the disorder; and epidemiological insights into its causation and pathogenesis.
This comprehensive volume, which includes discussions of therapeutic strategies that are currently used or under development, is a vital reference for neurobiologists, cell biologists, pathologists, and other scientists pursuing the biological basis of Alzheimer disease, as well as investigators, clinicians, and students interested in its pathogenesis, treatment, and prevention.
Contents
Preface
Deciphering Alzheimer Disease
Dennis Selkoe, Eckhard Mandelkow, and David Holtzman
The Clinical Problem of Symptomatic Alzheimer Disease and Mild Cognitive Impairment
Rawan Tarawneh and David M. Holtzman
The Neuropsychological Profile of Alzheimer Disease
Sandra Weintraub, Alissa H. Wicklund, and David P. Salmon
Neuropathological Alterations in Alzheimer Disease
Alberto Serrano-Pozo, Matthew P. Frosch, Eliezer Masliah, and Bradley T. Hyman
Brain Imaging in Alzheimer Disease
Keith A. Johnson, Nick C. Fox, Reisa A. Sperling, and William E. Klunk
Fluid Biomarkers in Alzheimer Disease
Kaj Blennow, Henrik Zetterberg, and Anne M. Fagan
Epidemiology of Alzheimer Disease
Richard Mayeux and Yaakov Stern
Biochemistry and Cell Biology of Tau Protein in Neurofibrillary Degeneration
Eva-Maria Mandelkow and Eckhard Mandelkow
Frontotemporal Dementia: Implications for Understanding Alzheimer Disease
Michel Goedert, Bernardino Ghetti, and Maria Grazia Spillantini
Biochemistry of Amyloid ß-Protein and Amyloid Deposits in Alzheimer Disease
Colin L. Masters and Dennis J. Selkoe
Trafficking and Proteolytic Processing of APP
Christian Haass, Christoph Kaether, Gopal Thinakaran, and Sangram Sisodia
Physiological Functions of APP Family Proteins
Ulrike C. Müller and Hui Zheng
The Genetics of Alzheimer Disease
Rudolph E. Tanzi
Presenilins and -Secretase: Structure, Function, and Role in Alzheimer Disease
Bart De Strooper, Takeshi Iwatsubo, and Michael S. Wolfe
Apolipoprotein E and Apolipoprotein E Receptors: Normal Biology and Roles in Alzheimer Disease
David M. Holtzman, Joachim Herz, and Guojun Bu
Animal Models of Alzheimer Disease
Frank M. LaFerla and Kim N. Green
Neurotoxicity of Amyloid ß-Protein: Synaptic and Network Dysfunction
Lennart Mucke and Dennis J. Selkoe
Inflammation in Alzheimer Disease—A Brief Review of the Basic Science and Clinical Literature
Tony Wyss-Coray and Joseph Rogers
The Ubiquitin–Proteasome System and the Autophagic–Lysosomal System in Alzheimer Disease
Yasuo Ihara, Maho Morishima-Kawashima, and Ralph Nixon
Proteolytic Degradation of Amyloid ß-Protein
Takaomi Saido and Malcolm A. Leissring
Neurovascular Dysfunction and Faulty Amyloid ß-Peptide Clearance in Alzheimer Disease
Abhay P. Sagare, Robert D. Bell, and Berislav V. Zlokovic
Treatment Strategies Targeting Amyloid ß-Protein
Dale Schenk, Guriqbal S. Basi, and Menelas N. Pangalos
Developing Therapeutic Approaches to Tau, Selected Kinases, and Related Neuronal Protein Targets
Virginia M.-Y. Lee, Kurt R. Brunden, Michael Hutton, and John Q. Trojanowski
Symptomatic and Nonamyloid/Tau Based Pharmacologic Treatment for Alzheimer Disease
Paul S. Aisen, Jeffrey Cummings, and Lon S. Schneider
Alzheimer Disease in 2020
David M. Holtzman, Eckhard Mandelkow, and Dennis J. Selkoe
Index