Advances in Drug Discovery for Alzheimer's Disease

Editor

Michael S. Wolfe (Editor)

ISBN: 9783032287298

Published: July 1, 2026

Format: Hardcover

Language: English

Publisher: Springer

Description

Volume 44 in the Topics in Medicinal Chemistry series brings together leading researchers to map the current state of drug discovery for Alzheimer’s disease, the condition responsible for the majority of dementia cases worldwide. Edited by Michael S. Wolfe, the Mathias P. Mertes Professor of Medicinal Chemistry at the University of Kansas, the volume examines medicinal-chemistry strategies aimed directly at amyloid-β and tau, the two proteins that pathologically accumulate in the Alzheimer’s brain, alongside indirect approaches that target the molecular chaperones and proteostasis machinery surrounding them. A closing chapter turns to artificial intelligence as a tool for drug repurposing, surveying how large-scale biomedical data is being mined to identify candidate compounds faster than traditional discovery pipelines allow.

Key Features

Seven peer-contributed chapters move from fundamentals to the drug-discovery frontier: a current-status overview by editor Michael S. Wolfe; recent advances in γ-secretase modulators; beta-secretase (BACE1) inhibitor programs; tau aggregation modulators; the role of molecular chaperones in tau proteostasis as a therapeutic opportunity in tauopathies; caspase-2 as a target for dementia; and an AI-driven drug-repurposing chapter. The content supports three concrete research applications: (1) triaging existing compound libraries against new Alzheimer’s targets before committing to synthesis; (2) benchmarking a lab’s own secretase or tau-aggregation program against the current competitive and mechanistic landscape; and (3) training graduate and postdoctoral researchers on how AI-assisted repurposing is reshaping neurodegenerative drug discovery.

Coverage

Amyloid-β-directed therapeutics (γ-secretase modulation, BACE1 inhibition); tau-directed therapeutics (aggregation modulators, molecular chaperones in tau proteostasis); caspase-2 as an emerging dementia target; artificial intelligence and big-data methods for drug repurposing in Alzheimer’s disease; and a critical appraisal of current and emerging drug candidates against the disease’s two defining pathologies.

About the Editor

Michael S. Wolfe is the Mathias P. Mertes Professor of Medicinal Chemistry at the University of Kansas, where he has worked since 2016. He began his academic career at the University of Tennessee, Memphis, in 1994, before moving to Harvard Medical School and Brigham and Women’s Hospital in 1999, where he was appointed Professor of Neurology in 2008. His research focuses on elucidating the molecular basis of Alzheimer’s disease and related disorders and identifying effective pharmacological interventions. He is the recipient of the MetLife Award for Biomedical Research (2008), the Zenith Fellows Award from the Alzheimer’s Association (2008), and the Potamkin Prize from the American Academy of Neurology (2009).

Table of Contents

1. Drug Discovery for Alzheimer’s Disease: Current Status — Michael S. Wolfe
2. Recent Advances in the Development of γ-Secretase Modulators to Treat Alzheimer’s Disease — Douglas S. Johnson, Martin Pettersson, Chenge Liu, Shekar Mekala, Yue-Ming Li
3. Beta-Secretase Inhibitors — Justyna A. Dobrowolska Zakaria, Robert J. Vassar
4. Tau Aggregation Modulators — Ibrar Siddique, Megan Hong, Gal Bitan
5. The Role of Molecular Chaperones in Tau Proteostasis: Potential Therapeutic Opportunities in Tauopathies — Aneta Grabinska-Rogala, Jason E. Gestwicki
6. Targeting Caspase-2 for the Treatment of Dementia — Michael A. Walters, Steffen Pockes, Karen H. Ashe
7. The Role of Artificial Intelligence for Drug Repurposing in Alzheimer’s Disease — Suman Guntupalli, Marina Bykova, William Martin, Feixiong Cheng

Why buy this book?

Alzheimer’s disease remains the leading cause of dementia worldwide, and the drug-discovery landscape is shifting quickly as amyloid- and tau-directed therapies move from the bench toward approved treatments. This volume gives medicinal chemistry, pharmacology, and neuroscience collections a single, current reference that connects mechanism to active drug-discovery programs, written by the researchers running them, including a dedicated look at how artificial intelligence is accelerating the search for new candidates. For academic and research libraries supporting pharmaceutical sciences, it is a direct addition to core holdings in neurodegenerative disease research.

Keywords

Alzheimer's disease, drug discovery, amyloid beta, tau aggregation, secretase inhibitors, BACE1 inhibitors, molecular chaperones, caspase-2, medicinal chemistry, neurodegenerative disease, pharmacology, dementia therapeutics, artificial intelligence drug repurposing

Target Audience

Medicinal chemists, pharmacologists, neuroscience researchers, pharmaceutical scientists, graduate and postdoctoral researchers, academic and medical research libraries

Genre

Pharmacology, Medicinal Chemistry, Neuroscience, Drug Discovery

Q&A

What is the current state of drug discovery for Alzheimer's disease?
Drug discovery for Alzheimer’s disease currently centers on two pathological proteins, amyloid-beta and tau, pursued through both direct approaches (secretase modulation, aggregation inhibitors) and indirect approaches (molecular chaperones, caspase-2 inhibition), alongside a growing role for AI-driven drug repurposing, as detailed in this volume edited by Michael S. Wolfe.

What are BACE1 inhibitors and why have they been difficult to develop?
BACE1 (beta-secretase) inhibitors block an enzyme required for amyloid-beta production. Chapter 3 of this volume, by Dobrowolska Zakaria and Vassar, reviews the inhibitor programs developed to date and the safety and efficacy challenges that have shaped the field.

How is artificial intelligence being used in Alzheimer's drug discovery?
AI and big-data methods are being applied to drug repurposing, mining existing compound libraries and biomedical datasets to identify candidates for Alzheimer’s disease faster than de novo discovery, a focus of the volume’s closing chapter by Guntupalli, Bykova, Martin, and Cheng.

What is the role of tau in Alzheimer's disease therapeutics?
Tau is one of the two proteins that pathologically accumulate in the Alzheimer’s brain. This volume covers tau aggregation modulators and the molecular chaperones that regulate tau proteostasis as two distinct therapeutic strategies.

Where can I buy Advances in Drug Discovery for Alzheimer's Disease?
Advances in Drug Discovery for Alzheimer’s Disease (Topics in Medicinal Chemistry, Vol. 44) is available for order directly through CLNZ Books, with worldwide shipping for academic and professional libraries.

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