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

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.

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Publication Details

Journal
Brain Health
Published
2026-01-13
DOI
https://doi.org/10.1002/brh2.70004
Primary Topic
Alzheimer's disease research and treatments
Type
article
Field-Weighted Citation Impact
0.00

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article

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

J. L. Shi, B. Vellas, Jeffery L. Cummings, Jacques Touchon
Brain Health
Alzheimer's disease research and treatments
article

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

J. L. Shi, B. Vellas, Jeffery L. Cummings, Jacques Touchon
article en

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.

Brain HealthVol. 1(1)
University of Science and Technology of China (CN), University of Nevada, Las Vegas (US), Université Toulouse III - Paul Sabatier (FR), Inserm (FR), Université Fédérale de Toulouse Midi-Pyrénées (FR), Université de Montpellier (FR), Centre Hospitalier Universitaire de Toulouse (FR), Centre Hospitalier Universitaire de Montpellier (FR), Centre de recherche en Epidémiologie et Santé des Populations (FR), Montpellier Business School (FR)
Alzheimer's Drug Discovery Foundation, Fundamental Research Funds for the Central Universities, National Institute on Aging, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke
Openalex Percentile: Top 89%
Alzheimer's disease research and treatments
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