Understanding the complexities of Alzheimer's disease, advancing biomarker discovery, and accelerating clinical research through data-driven approaches
Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia, affecting millions worldwide. It is characterized by the accumulation of abnormal protein deposits in the brain, leading to neuronal death and cognitive decline.
The disease typically progresses through stages, beginning with mild memory loss and eventually affecting the ability to carry out daily activities. Early detection through biomarkers is crucial for intervention and management.
Genetic Factors: Mutations in APP, PSEN1, and PSEN2 genes cause early-onset AD. The APOE-e4 allele increases risk for late-onset AD.
Age: The greatest risk factor, with prevalence doubling every 5 years after age 65.
Other Factors: Cardiovascular health, education level, traumatic brain injury, lifestyle factors, and comorbid conditions all influence AD risk.
Research is focused on multiple therapeutic targets including anti-amyloid therapies (aducanumab, lecanemab), tau-targeting approaches, anti-inflammatory strategies, and neuroprotective agents.
Recent Advances: FDA approval of lecanemab (2023) and donanemab showing promise in reducing amyloid plaques and slowing cognitive decline in early-stage AD.
Emerging areas include blood-based diagnostics, precision medicine approaches, and multi-modal interventions targeting lifestyle factors.
Currently, there is no cure for Alzheimer's disease. Available treatments can temporarily slow symptom progression but cannot stop or reverse the underlying disease process.
Approved Treatments: Cholinesterase inhibitors (donepezil, rivastigmine) and NMDA antagonists (memantine) provide symptomatic relief. Disease-modifying therapies like lecanemab show modest benefits in early stages.
The path to a cure requires better understanding of disease mechanisms, earlier detection, and combination therapies targeting multiple pathways.
Difficulty identifying and enrolling appropriate participants, especially in early disease stages requiring biomarker screening
AD manifests differently across individuals, making it challenging to design trials with uniform outcomes and response criteria
Slow disease progression requires long trials with sensitive cognitive and functional endpoints
Biomarker Requirements: Many trials now require biomarker confirmation (amyloid-positive), limiting eligible populations and increasing costs
High Failure Rate: Over 99% of AD trials have failed historically, highlighting the complexity of the disease
Long Duration: Trials often span 18-36 months, requiring sustained participant commitment and substantial funding
Ethical Considerations: Use of placebo in trials when disease-modifying treatments emerge, informed consent in cognitively impaired populations
Leisgang Osse, Zhou, Kinney, Fonseca, Cheng, Cummings & colleagues examine biomarker utilization across all active Alzheimer's disease-targeted therapeutic trials on ClinicalTrials.gov. Biomarkers are incorporated in 84% of trials — as inclusion criteria in 58% and as primary outcome measures in 36%. Usage is highest in Phase 2 (91%) and reflects the growing centrality of biomarker-driven trial design.
Alzheimer's & Dementia: Translational Research & Clinical Interventions (2026) →The 2025 pipeline report by Cummings, Zhou, Lee, Zhong, Fonseca, Leisgang-Osse & Cheng documents 138 drugs in 182 clinical trials, with 31 agents in Phase 3, 75 in Phase 2, and 45 in Phase 1. Biomarkers are among the primary outcomes of 27% of active trials. The pipeline now requires over 50,000 participants globally.
Alzheimer's & Dementia: Translational Research & Clinical Interventions (2025) →Presented at the Alzheimer's Association International Conference (AAIC 2025), the Biomarker Observatory is an AI-powered platform for systematically monitoring biomarker use across clinical trials registered on ClinicalTrials.gov, providing researchers a comprehensive, continuously updated repository of advancements in AD biomarker science.
Alzheimer's & Dementia, AAIC 2025 Abstract →Second anti-amyloid antibody approved for early Alzheimer's, showing 35% slowing of decline in Phase 3 trials. Together with lecanemab, these disease-modifying therapies represent a new era of treatments targeting amyloid pathology.
Plasma p-tau217 shows over 90% accuracy in detecting AD pathology, potentially revolutionizing early screening. The Alzheimer's Association has issued clinical practice guidelines for blood-based biomarker use in specialized care settings.
Disease-targeted therapies now address 15 distinct biological processes via CADRO classification. Neurotransmitter receptors (22%), amyloid-beta pathways (18%), and neuroinflammation (17%) are the most represented targets. Repurposed agents account for 33% of the pipeline, and 62% of trials are industry-sponsored.
FINGER study shows multi-domain interventions (diet, exercise, cognitive training) can reduce dementia risk in at-risk populations
The Alzheimer's Drug Discovery Foundation (ADDF) has funded the creation of the Biomarker Observatory — a first-of-its-kind initiative led by Dr. Jeffrey Cummings (UNLV) and Dr. Feixiong Cheng (Cleveland Clinic). Described as "the natural counterpart to the clinical trial report," the Observatory provides researchers a comprehensive, continuously updated repository of biomarker advancements across blood tests, brain imaging, and digital diagnostic tools.
This complements the ADDF's Diagnostics Accelerator program, which has invested over $60 million in 70+ projects since 2018 to advance biomarker science. The Observatory aims to fill gaps in the biomarker pipeline, accelerate novel drug development including combination therapies, and enable precision medicine approaches for Alzheimer's disease.
Launched by the NIH and HHS, with updated goals to prevent and effectively treat AD by 2025 (extended to 2030s due to complexity).
Genetic and molecular mechanisms
Early detection and diagnostics
Drug development pipelines
Health disparities research
Neuroinflammation and immunity
Big data and AI applications
Blood-based biomarker standardization
Precision medicine & combination therapies
Source: Cummings et al. (2025)
If you or a loved one is living with Alzheimer's disease, you don't have to wait. Hundreds of clinical trials are actively enrolling patients — each one a real opportunity to access the latest treatments and contribute to the science that will help future generations.
Learn More & Find Trials Near You →The Alzheimer's Disease Biomarker Observatory (ADBMO) is a comprehensive platform designed to accelerate biomarker discovery and clinical trial analysis through AI-powered annotation and data integration.
Access biomarker tree visualization, trial trackers, and weekly updates on Alzheimer's research developments
LLM + string matcher annotation tool for clinical trials using dual-LLM biomarker extraction with AT(N) framework mapping
AI-powered chatbot for Alzheimer's research questions, biomarker information, and clinical trial guidance
Clinical trial tracker with weekly ClinicalTrials.gov diffs and biomarker-aware monitoring
News aggregator for Alzheimer's research developments, FDA updates, and clinical trial results
Biomarker tree management tools for curating and organizing the AT(N) knowledge hierarchy
Interactive data analyses with figures, tables, and visualizations from our research databases
Live mirror of ClinicalTrials.gov — daily change detection, version history, and NDD cohort surveillance