SEOUL — Research into Alzheimer's disease is expanding its targets beyond beta-amyloid proteins to include brain inflammation and energy metabolism, a shift reflected in global clinical trials. Professor Paul Matthews of Imperial College London will outline how these factors converge to drive neuronal injury in early Alzheimer's at the Healthcare Innovation Forum in Seoul in December 2026. An analysis published in May found that, as of Jan. 1, 2024, 192 clinical trials were testing 158 Alzheimer's drug candidates worldwide. Candidates targeting inflammation and immune function rose from about 6% in 2016 to about 20% this year, while those targeting beta-amyloid fell from about 33% to 20%. "The trend shows Alzheimer's drug development is moving beyond amyloid-centered approaches to target multiple disease pathways," according to the analysis in Alzheimer's & Dementia: Translational Research & Clinical Interventions.
Matthews, who directs the Rosalind Franklin Institute and heads the Imperial group of the UK Dementia Research Institute, is a leading scholar connecting vascular dysfunction, inflammation and energy deficits. His team's 2024 study in Nature Communications compared brain tissue from Alzheimer's patients and healthy individuals, analyzing gene expression in cerebrovascular cells. The research found that inflammatory responses in endothelial cells and abnormalities in vascular regeneration are linked to blood-brain barrier disruption. The study suggested that modulating cerebrovascular inflammation and restoring damaged vascular function could be a new therapeutic strategy for Alzheimer's. In 2025, the team published in the same journal an analysis of why certain neurons are more vulnerable to damage than others. In temporal lobe tissue, they confirmed that a subset of neurons with intracellular beta-amyloid accumulation were more prone to degeneration, with activated microglia densely distributed around these cells. Matthews has also studied the brain's energy production, with a 2022 study in Science Translational Medicine using PET scans to identify mitochondrial dysfunction and cellular stress patterns in the brains of patients with early Alzheimer's. That work provided evidence that energy metabolism abnormalities can appear from the earliest stages of the disease.
Existing Alzheimer's treatments include antibody therapies like Leqembi and Kisunla, which clear beta-amyloid and slow progression but are used only in early-stage patients. These drugs can cause amyloid-related imaging abnormalities, including brain edema and microhemorrhages, requiring close monitoring. Academia is now focusing on immune responses, vascular function and energy metabolism abnormalities that contribute to neuronal damage. Microglia, the brain's immune cells, can trigger harmful inflammation when excessively activated, while declining mitochondrial function can disrupt normal neuronal activity.
Matthews will deliver a keynote at HIF 2026 on Dec. 4 titled "A double hit to the brain: inflammation and energy failure in Alzheimer's and multiple sclerosis." He is expected to explain how neuroinflammation and energy metabolism deficits impair brain function, drawing on research in both conditions. The session will highlight the research trend of seeking new strategies to slow or prevent Alzheimer's beyond amyloid removal. The forum will be held at the Grand Ballroom of The Westin Josun Seoul in Jung-gu, Seoul.