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Recent Insights Into Alzheimer's Disease: Advances in Pathophysiology and Therapeutic Strategies

Year: 2026

Type: article

Abstract: ABSTRACT Alzheimer's disease (AD) is a complex neurodegenerative disorder driven by interplay among amyloid‐β (Aβ) plaques, tau neurofibrillary tangles, inflammation and comorbid pathologies. Recent advances in biomarkers and therapeutic approvals have reshaped our understanding of its pathophysiology and treatment landscape. This paper synthesizes evidence on the temporal dynamics of Aβ and tau deposition, highlighting tau's role as a key mediator of cognitive decline and the threshold‐dependent effects of Aβ. It explores how comorbidities—including vascular injury, neuroinflammation, and proteinopathies overlaps—modulate disease progression and response to therapy. Despite uncertainty about early anti‐Aβ approaches, recent monoclonal antibody trials (e.g., lecanemab, donanemab) demonstrate clinical benefit, underscoring the importance of early intervention. These agents require risk mitigation to avoid or manage amyloid‐related imaging abnormalities (ARIA). Emerging strategies emphasize precision medicine, targeting tau pathology and comorbid mechanisms to address the heterogeneous nature of AD. Integrating multi‐modal biomarkers and adaptive trial designs will be critical to developing effective, personalized therapies.

Source: Brain Health

DOI: 10.1002/brh2.70004

Authors: Jiong Shi, Jeffery Cummings, Jacques Touchon, Bruno Vellas