Nonamyloid-beta active immunization for the treatment of Alzheimer's disease

Authors

Olivia Triplett, University of Arizona College of Medicine, Phoenix, AZ, USA.
Nicole Varda, University of Arizona College of Medicine, Phoenix, AZ, USA.
Boris Decourt, Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX, USA.
Marwan N. Sabbagh, Department of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA.

Document Type

Article

Abstract

INTRODUCTION: Alzheimer's disease (AD) is characterized by the formation of senile plaques composed of amyloid-beta (Aβ) peptides and the intraneuronal accumulation of neurofibrillary tangles composed of abnormal, hyperphosphorylated tau proteins. These act in concert to drive cognitive decline, but it is widely held that tau spread correlates better with cognitive decline than does amyloid burden. Control of AD neuropathologies with active immunizations is studied as a potential therapeutic avenue because it could build innate immunity. Although most active immunization studies have focused on Aβ targets, tau and other targets continue to be explored. AREAS COVERED: This study aimed to identify and describe non-Aβ active immunization trials for AD treatment. A narrative review was conducted to analyze the current status of non-Aβ active immunization for AD using PubMed as the research database. EXPERT OPINION: The potential of active immunization beyond Aβ was explored as a therapeutic strategy for AD with a focus that targets tau and provides insights into its effectiveness, associated challenges, and limitations. Results from preclinical and clinical studies were examined, highlighting the progress and the hurdles that exist. Active immunization against non-Aβ targets, such as tau, for the treatment of AD remains a promising and expanding field.

Medical Subject Headings

Alzheimer Disease (therapy, immunology, physiopathology); Humans; Animals; tau Proteins (immunology, metabolism); Amyloid beta-Peptides (immunology, metabolism); Cognitive Dysfunction (therapy, immunology); Immunotherapy, Active (methods); Immunity, Innate (immunology); Alzheimer Vaccines (administration & dosage, immunology); Immunization (methods)

Publication Date

9-1-2025

Publication Title

Expert opinion on investigational drugs

E-ISSN

1744-7658

Volume

34

Issue

9

First Page

685

Last Page

693

PubMed ID

40842219

Digital Object Identifier (DOI)

10.1080/13543784.2025.2551352

Recommended Citation

Triplett, Olivia; Varda, Nicole; Decourt, Boris; and Sabbagh, Marwan N., "Nonamyloid-beta active immunization for the treatment of Alzheimer's disease" (2025). Neurology. 2040.
https://scholar.barrowneuro.org/neurology/2040