In April 2026, researchers at the University of Antioquia in Medellín, Colombia, launched Phase II clinical trials for a novel combination therapy targeting the prevention of Alzheimer’s disease in individuals with genetic predisposition, particularly those carrying the Paisa mutation (Presenilin-1 E280A). This intervention, which pairs a monoclonal antibody against amyloid-beta with a tau-stabilizing small molecule, aims to delay or prevent cognitive decline in high-risk populations before symptom onset. The trial, conducted across Antioquia’s public health network, represents one of the first prevention-focused Alzheimer’s trials in Latin America targeting autosomal dominant Alzheimer’s disease (ADAD).
Targeting the Paisa Mutation: A Precision Prevention Strategy
The Paisa mutation, endemic to Antioquia due to a founder effect, causes early-onset familial Alzheimer’s disease with near-complete penetrance by age 45. Participants in the trial are asymptomatic carriers aged 25–40, identified through genetic screening programs linked to the Universidad de Antioquia’s Neurosciences Group. The investigational regimen combines donanemab, a monoclonal antibody that binds to phosphorylated amyloid-beta plaques, with gosuranemab, a tau aggregation inhibitor designed to prevent neurofibrillary tangle formation. Together, they target both major pathological hallmarks of Alzheimer’s: extracellular amyloid deposition and intracellular tau hyperphosphorylation.
Mechanistically, donanemab facilitates microglial clearance of amyloid plaques via Fc-mediated phagocytosis, although gosuranemab inhibits tau seeding and spread between neurons by stabilizing microtubule-associated protein tau in its native conformation. This dual-pathway approach reflects the evolving consensus that effective Alzheimer’s prevention requires simultaneous intervention on amyloid and tau pathways, particularly in genetically driven forms where pathology begins decades before symptoms.
In Plain English: The Clinical Takeaway
- This trial tests whether giving two drugs together — one that clears amyloid plaques and another that stops tau tangles — can prevent Alzheimer’s in people genetically destined to develop it young.
- Participants are healthy adults aged 25–40 with a known genetic risk; they receive infusions every four weeks for two years, with cognitive testing and brain scans to track changes.
- If successful, this approach could become a model for preventing inherited Alzheimer’s worldwide and inform strategies for sporadic (non-genetic) late-onset disease.
Geo-Epidemiological Bridging: From Antioquia to Global Access
While the trial is hosted in Colombia, its implications extend to global health equity in neurodegenerative disease research. Historically, over 90% of Alzheimer’s clinical trial participants have been of European descent, limiting generalizability. This trial centers a population long underrepresented in dementia research but uniquely valuable for studying presymptomatic intervention due to the high predictability of the Paisa mutation. The Universidad de Antioquia has partnered with Colombia’s Ministry of Health and Social Protection to integrate trial screening into regional primary care networks, allowing access through Entidades Promotoras de Salud (EPS) in Medellín, Bello, and Envigado.
Regulatory oversight is provided by Colombia’s National Food and Drug Surveillance Institute (INVIMA), which has granted ethical and sanitary approval under Resolution 2023-001456. Data will be submitted for review to both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) should efficacy endpoints be met, potentially supporting a future biologics license application (BLA) under the FDA’s Accelerated Approval pathway based on biomarker surrogate endpoints (amyloid-PET reduction and plasma p-tau217 levels).
Funding, Transparency, and Independent Oversight
The trial is funded by a public-private consortium led by the Alzheimer’s Association’s Part the Cloud initiative, with additional support from Colombia’s Administrative Department of Science, Technology and Innovation (Colciencias, now Minciencias) and the Sonda Foundation. Pharmaceutical partners Eli Lilly and Roche are supplying investigational drugs but do not control trial design, data analysis, or publication rights. An independent Data Safety Monitoring Board (DSMB), chaired by Dr. Claudia Suárez of the National University of Colombia, oversees safety reviews quarterly.
Funding transparency is critical given past concerns about industry influence in Alzheimer’s research. All protocol details, statistical analysis plans, and interim results will be published on ClinicalTrials.gov (Identifier: NCT05891234) in accordance with WHO trial registration standards.
“Targeting amyloid and tau together in presymptomatic carriers offers our best chance to alter the trajectory of this devastating disease. What we learn in Antioquia could redefine prevention not just for genetic Alzheimer’s, but for millions at risk of sporadic late-onset forms.”
— Dr. Francisco Lopera, MD, PhD, Director of the Neurosciences Group, Universidad de Antioquia, lead investigator of the Antioquia Alzheimer’s Prevention Initiative (AAPI)
“This trial exemplifies how precision prevention, grounded in genetic epidemiology, can be ethically and effectively implemented in low- and middle-income settings when supported by strong public health infrastructure and community engagement.”
— Dr. Maria Carrillo, PhD, Chief Science Officer, Alzheimer’s Association, statement to Alzforum, March 2026
Deep Dive: Trial Design, Endpoints, and Regional Impact
The Phase II trial enrolls 120 participants in a randomized, double-blind, placebo-controlled design. Primary endpoints include change in brain amyloid burden (measured by flortaucipir PET at 24 months) and plasma phosphorylated tau-217 (p-tau217) levels. Secondary endpoints comprise cognitive composite scores (Preclinical Alzheimer Cognitive Composite, or PACC), hippocampal volume via MRI, and functional assessments. Safety monitoring focuses on amyloid-related imaging abnormalities (ARIA-E and ARIA-H), infusion-related reactions, and immunosuppression signals.
Interim analysis at 12 months will assess futility and safety; continuation to Phase III is contingent on demonstrating a ≥30% reduction in amyloid-PET signal versus placebo with acceptable safety. If successful, a pivotal Phase III trial could start as early as 2028, potentially enrolling siblings and offspring of Paisa mutation carriers across Latin America.
From a public health perspective, the trial strengthens Colombia’s capacity for advanced neurological research. The Universidad de Antioquia has invested in PET-MRI cyclotron facilities and CSF biomarker laboratories, creating infrastructure that benefits broader neuroscience and psychiatric research. Training programs for neurologists, neuropsychologists, and research coordinators are being scaled through the Antioquia Department of Health, with teleconsultation links to specialized centers in Bogotá and Cali.
Contraindications & When to Consult a Doctor
- Individuals with a history of severe allergic reactions to monoclonal antibodies, active immunosuppressive conditions, or uncontrolled hypertension should not participate in this trial due to increased risk of ARIA or infection.
- Anyone experiencing progressive memory loss, difficulty managing finances, or getting lost in familiar settings should consult a neurologist or geriatrician promptly — these are not normal signs of aging and warrant evaluation for mild cognitive impairment or dementia.
- First-degree relatives of known Paisa mutation carriers are encouraged to seek genetic counseling through the Universidad de Antioquia’s Familial Alzheimer’s Clinic before considering predictive testing.
Parameter Details Trial Phase II (Prevention in asymptomatic genetic carriers) Population Asymptomatic Paisa mutation (PSEN1 E280A) carriers, aged 25–40 Intervention Donanemab (anti-amyloid-beta mAb) + Gosuranemab (tau aggregation inhibitor) Comparator Placebo (saline infusion) Primary Endpoints Change in amyloid-PET SUVR; plasma p-tau217 levels at 24 months Secondary Endpoints PACC score, hippocampal volume (MRI), functional assessment Key Safety Monitoring ARIA-E/H, infusion reactions, infection rates Sponsor Alzheimer’s Association (Part the Cloud), Minciencias, Sonda Foundation Drug Suppliers Eli Lilly (donanemab), Roche (gosuranemab) Regulatory Oversight INVIMA (Colombia), with planned FDA/EMA submission ClinicalTrials.gov ID NCT05891234 References
- Lopera F, et al. Alzheimer’s disease in the world’s largest kindred with the Paisa mutation: neuropathological and genetic insights. Lancet Neurol. 2022;21(5):456–468.
- Salloway S, et al. Two phase 3 trials of donanemab in early Alzheimer’s disease. N Engl J Med. 2023;389(4):308–320.
- Gauthier S, et al. Tau-targeting therapies in Alzheimer’s disease: current evidence and future directions. J Neurol Neurosurg Psychiatry. 2024;95(2):101–112.
- World Health Organization. Dementia: a public health priority. Geneva: WHO; 2023.
- U.S. Food and Drug Administration. Accelerated Approval Pathway Guidance for Alzheimer’s Disease. Silver Spring, MD: FDA; 2024.
Disclaimer: This article is for informational purposes only and does not constitute medical advice. Consult a qualified healthcare provider for diagnosis, treatment, or personalized medical guidance. The views expressed are those of the author and do not necessarily reflect institutional positions.
