Alzheimer Disease: New Brain Targets and the New Drug Pipeline
Among 180+ active AD trials, 15 biological targets span traditional Aβ and tau proteins as well as new pathways in brain metabolism, neuroinflammation, and synaptic health.
Research on Alzheimer disease (AD) is in a pivotal stage, marked by an accelerating shift from symptom management to therapies that target the underlying biology of neurodegeneration. In 2025, the therapeutic landscape is broader and more diverse than at any point in the past, reflecting a recognition that Alzheimer’s cannot be addressed through a single pathway. More than 180 clinical trials are currently active, spanning 15 distinct biological targets that include not only the familiar amyloid and tau proteins, but also brain metabolism, neuroinflammation, and synaptic health.1 This diversification underscores a deepening understanding of disease mechanisms and is creating opportunities for more tailored interventions.
Disease-modifying therapies are beginning to demonstrate measurable clinical benefit. The approvals of lecanemab and donanemab established proof of principle that cognitive decline can be slowed, even if modestly, in early-stage patients. The progress these advances reflect can't be overstated after decades in which treatment was limited to cholinesterase inhibitors and NMDA receptor antagonists. At the same time, innovative approaches such as Roche’s trontinemab, designed with enhanced blood–brain barrier penetration technology,2 are opening new avenues for more effective delivery of monoclonal antibodies. The promise of the next-gen platforms is underscored by early findings that point to substantial amyloid clearance.
The pipeline is also being enriched by drug repurposing strategies. Approximately 30% of candidates in development originated in other therapeutic areas, including diabetes and cardiovascular disease.1 For example, the GLP-1 receptor agonist semaglutide is being evaluated for effects on brain inflammation and metabolism, particularly in early stage symptomatic AD.3 There is potential for the dual approach, ie, novel mechanisms alongside repurposed agents, to accelerate timelines and reduce cost while also expanding therapeutic possibilities.
The disease targets and investigational agents mentioned in the short slide show above are by no means an exhaustive accounting the depth and breadth of current development programs, but the at-a-glance format is ideal for busy office-based primary care clinicians who need to looking for a quick refresher. Check the references below for a more detailed scope.
References
Cummings JL, Zhou Y, Lee G, et al. Alzheimer's disease drug development pipeline: 2025. Alzheimer’s Dement. 2025;11:e70098.
doi:10.1002/trc2.70098Roche presents new insights in Alzheimer’s disease research across its diagnostics and pharmaceutical portfolios at AAIC. News release. Roche. July 27, 2025. Accessed September 17, 2025. https://www.roche.com/investors/updates/inv-update-2025-07-28
Cummings JL, Atri A, Feldman HH, et al. evoke and evoke+: design of two large-scale, double-blind, placebo-controlled, phase 3 studies evaluating efficacy, safety, and tolerability of semaglutide in early-stage symptomatic Alzheimer's disease. Alzheimers Res Ther. 2025;17(1):14. doi: 10.1186/s13195-024-01666-7.
