Therapy for Alzheimer's disease: Missing targets and functional markers?

Area of Science:

• Neuroscience
• Pharmacology
• Biomarker Discovery

Background:

• Alzheimer's disease (AD) therapy development faces significant hurdles, with many drug candidates failing despite increased understanding of the disease.
• Recent advancements in genetics, pathophysiology, and clinical characteristics offer new insights but require updated research strategies.

Purpose of the Study:

• To review current concepts and controversies in developing disease-modifying and symptomatic treatments for Alzheimer's disease.
• To explore updated AD research strategies, including broadened drug targets and non-pharmacological interventions.
• To discuss the role of established and novel biomarkers in assessing disease progression and treatment efficacy.

Main Methods:

• Literature review of recent advancements in Alzheimer's disease research.
• Analysis of current therapeutic development strategies and challenges.
• Discussion of various biomarker types, including fluid (CSF, plasma), neuroimaging, and neurophysiological markers.

Main Results:

• Emerging fluid biomarkers (CSF, plasma) show potential for detecting tau pathology, neuroinflammation, and neurodegeneration.
• Neuroimaging and neurophysiological biomarkers offer objective assessments of brain changes and neural network integrity.
• A combination of multiple biomarkers, including target engagement and outcome measures, is crucial for advancing translational studies.

Conclusions:

• Successful development of next-generation Alzheimer's disease therapies requires innovative strategies and a multifaceted approach to biomarker utilization.
• Integrating various biomarkers can enhance the evaluation of treatment efficacy and facilitate the development of effective interventions for AD.
• Future research should focus on combining different biomarker modalities to improve translational success in AD drug development.