Preface; Contents; Targets and Strategies Toward the Development of Alzheimer Therapeutics; 1 Introduction; 2 AD Presentation and Progression; 3 Pathology; 3.1 Amyloid; 3.2 Tau; 3.3 Neuroinflammation; 4 Pathogenesis and Risk Factors; 5 Animal Models; 6 Clinical Trials; 7 Therapeutic Targets and Strategies; 7.1 Symptomatic Treatment; 7.2 Targeting Abeta; 7.2.1 beta-Secretase Inhibitors; 7.2.2 gamma-Secretase Modulators; 7.2.3 Aggregation Inhibitors; 7.3 Targeting Tau; 7.3.1 Aggregation Inhibitors; 7.3.2 Kinase Inhibitors; 7.3.3 Microtubule Stabilizers; 7.3.4 Increasing Clearance

7.4 Targeting ApoE8 Imaging Agents; 8.1 Amyloid; 8.2 Tau; 9 Perspective; References; The Design, Development, and Evaluation of BACE1 Inhibitors for the Treatment of Alzheimerś Disease; 1 Introduction; 1.1 The Amyloid Hypothesis of AD; 2 BACE1 as a Target for AD; 3 Evolution of BACE1 Inhibitors; 3.1 Structure-Based Design of Inhibitors; 3.2 Design of Peptidomimetic Inhibitors; 3.2.1 Hydroxyethylene-Based Inhibitors; 3.2.2 Hydroxyethylamine-Based Inhibitors; 3.2.3 Carbinamine-Based Inhibitors; 3.2.4 Reduced Amide-Based Inhibitors; 3.2.5 Macrocyclic Peptidomimetic Inhibitors

3.3 Nonpeptide Inhibitors3.3.1 Acyl Guanidine-Based Inhibitors; 3.3.2 2-Aminopyridine-Based Inhibitors; 3.3.3 Aminoimidazole-Based Inhibitors; 3.3.4 Aminohydantoin-/Iminohydantoin-Based Inhibitors; 3.3.5 Aminothiazoline- and Aminooxazoline-Based Inhibitors; 3.3.6 Dihydroquinazoline-Based Inhibitors; 3.3.7 Aminoquinoline-Based Inhibitors; 3.3.8 Pyrrolidine-Based Inhibitors; 3.3.9 Macrocyclic Nonpeptide Inhibitors; 4 Clinical Evaluation of BACE1 Inhibitors; 4.1 Clinical Evaluation of CTS21166; 4.2 Clinical Evaluation of LY2811376; 4.3 Clinical Evaluation of LY2886721

4.4 Clinical Evaluation of E26094.5 Clinical Evaluation of AZD3839; 4.6 Clinical Evaluation of RG7129; 4.7 Clinical Evaluation of PF-05297909; 4.8 Clinical Evaluation of HPP854; 4.9 Clinical Evaluation of MK-8931; 4.10 Clinical Evaluation of AZD3293; 4.11 Clinical Evaluation of JNJ-54861911; 4.12 Clinical Evaluation of VTP-37948; 4.13 Clinical Evaluation of CNP520; 5 Conclusions and Outlook; References; gamma-Secretase Modulators as Abeta42-Lowering Pharmacological Agents to Treat Alzheimerś Disease; 1 Introduction; 2 gamma-Secretase Modulators; 2.1 Acid gamma-Secretase Modulators

2.2 Heterocyclic gamma-Secretase Modulators2.3 Natural Product-Derived gamma-Secretase Modulators; 3 Summary; References; Inhibitors of Tau-Phosphorylating Kinases; 1 Alzheimerś Disease (AD); 1.1 Epidemiology; 1.2 Symptoms and Disease Progression; 1.3 Causes of AD; 1.4 AD Aetiology; 1.4.1 Cholinergic Hypothesis; 1.4.2 Glutamatergic Hypothesis; 1.4.3 Amyloid Hypothesis; 1.4.4 Tau Hypothesis; 1.5 Current Treatment of AD; 2 Implications of Tau Phosphorylation in AD; 3 Kinases Involved in Tau Phosphorylation; 3.1 Proline-Directed Protein Kinases, PDPKs; 3.1.1 GSK3; 3.1.2 CDK5; 3.1.3 MAPK; P38