Researchers from the Cleveland Alzheimer's Disease Research Center (CADRC) continue to make important contributions to Alzheimer's disease research, with two recent publications led by CADRC Director Jagan A. Pillai, MD, PhD highlighting advances in both early disease detection and the future of clinical trials.

Identifying Early Biomarkers of Alzheimer's Disease

In a study published in September 2026, Dr. Pillai and colleagues examined biological markers associated with Alzheimer's disease in cognitively normal older adults who were at increased risk for developing the disease.

The two-year longitudinal study followed 118 adults between the ages of 65 and 80 and included a comprehensive analysis of more than 1,300 cerebrospinal fluid (CSF) proteins and 1,500 plasma analytes. Researchers investigated how changes in these biological markers relate to Alzheimer's pathology and future cognitive decline.

The study identified inflammatory pathways and complex network alterations associated with Alzheimer's disease pathology and longitudinal cognitive decline. Among the findings, the inflammatory molecule eotaxin-1 was identified as a biomarker associated with Alzheimer's disease pathology and cognitive decline.

Because Alzheimer's disease can begin affecting the brain years or even decades before memory loss becomes apparent, identifying reliable early biomarkers is critical. Findings from this work may help enable earlier risk assessment, improve clinical trial design, and support the development of targeted interventions to protect cognitive health as people age.

CADRC investigators contributing to the study included Dr. Pillai, Steven Rao, PhD, Feixiong Cheng, PhD, Frank P. DiFilippo, PhD, and Lynn Bekris, PhD.

Preparing Alzheimer's Clinical Trials for a New Era of Treatment

A second publication, also released in September 2026, explores how Alzheimer's disease clinical trials must evolve as targeted therapies become more widely available.

In the perspective article, Operationalizing Alzheimer's Disease Trials in the Era of Targeted Therapies, Dr. Pillai and co-authors discuss the opportunities and challenges created by the clinical adoption of anti-amyloid monoclonal antibody treatments.

The article discusses challenges that must be considered when designing the next generation of Alzheimer's disease clinical trials, including limited population diversity in research studies, variations in healthcare access, and unrecognized co-pathologies that may affect the generalizability of trial results.

The paper supports the use of multi-domain biomarkers together with real-world clinical outcomes in future observational and therapeutic studies. This approach could help move the field toward more personalized, mechanism-driven, and effective therapeutic approaches for Alzheimer's disease.

Contributing CADRC investigators included Dr. Pillai, Brian Appleby, MD, and Babak Tousi, MD.

Advancing the Future of Alzheimer's Research

Together, these publications highlight complementary efforts at the CADRC to advance Alzheimer's disease research, from identifying biomarkers associated with disease pathology and cognitive decline to informing the design of future observational studies and clinical trials. By deepening our understanding of disease-related biomarkers and helping shape the next generation of clinical trials, CADRC investigators continue to advance research that may ultimately improve outcomes for individuals affected by Alzheimer's disease and related dementias.