Study Led from Valdecilla Identifies Early Alzheimer’s Signals in Glial Cells Before the First Memory Failures

The research, awarded and presented at international scientific forums, paves the way for new strategies in early detection and prevention of the disease.

A study led by the Cognitive Impairment Unit at Marqués de Valdecilla University Hospital (HUMV) and the Marqués de Valdecilla Research Institute (IDIVAL) has shown that glial cells—microglia and astrocytes—display activation signs in the very early stages of Alzheimer’s disease, even before the first memory problems appear. These findings open the door to new strategies for early diagnosis and prevention.

The research, published in the prestigious journal Alzheimer’s & Dementia, was led by Dr. Marta Fernández-Matarrubia, together with a multidisciplinary team from the Cognitive Impairment Unit of the HUMV Neurology Service and the Immunology Service, in collaboration with researchers from the University of Gothenburg (Sweden). This study was made possible thanks to funding from IDIVAL through its Emerging Researcher Support Program.

The role of brain inflammation in the initial stages of Alzheimer’s is still not fully understood. Glial cells are essential for maintaining nervous system balance, but in situations of chronic brain inflammation, they may contribute to dysfunction and neuronal loss. The aim of this study was to simultaneously analyze various biomarkers of astrocytes and microglia, and their relationship with the earliest changes in the disease.

To this end, 211 cognitively healthy volunteers from the Autonomous Community were studied, all part of the “Valdecilla Cohort for the Study of Memory and Brain Aging.” Blood and cerebrospinal fluid samples were collected from all participants.

Key Findings

• The astrocyte marker GFAP, measured in plasma, rises in very early stages and is directly associated with the accumulation of beta-amyloid in the brain.
• The microglial marker sTREM2 is linked to the development of tau pathology, another key protein in Alzheimer’s.
• Other astroglial markers, such as YKL-40 and S100β, are related to later neurodegenerative changes, consistent with the amyloid cascade hypothesis.

These data confirm that glial reactivity is an early phenomenon influencing the pathological sequence of Alzheimer’s—from amyloid accumulation to neuronal degeneration.

Clinical Implications

Detecting these changes through fluid analysis could make it possible to identify people at risk many years before symptoms appear, contribute to risk stratification, and facilitate disease monitoring. This could open new opportunities for preventive clinical trials and for evaluating the efficacy of future treatments.

The project has achieved notable scientific visibility: its results were presented at the 2024 Annual Meeting of the Spanish Society of Neurology, where Dr. Fernández-Matarrubia received the award for Best Oral Communication in the Dementia category, and it has been accepted for presentation at the 18th Clinical Trials on Alzheimer’s Disease (CTAD) international conference, to be held in San Diego, California (USA), from December 1–4, 2025.

Next Steps

The team will continue the longitudinal follow-up of participants to analyze the evolution of these biomarkers and their ability to predict clinical development. They also plan to combine these data with advanced neuroimaging techniques to more precisely map the progression of preclinical Alzheimer’s.

Article Reference:
Fernández-Matarrubia M, Valera-Barrero A, Renuncio-García M, Aguilella M, Lage C, López-García S, Ocejo-Vinyals JG, Martínez-Dubarbie F, Molfetta GD, Pozueta-Cantudo A, García-Martínez M, Corrales-Pardo A, Bravo M, López-Hoyos M, Irure-Ventura J, Blennow K, Ashton NJ, Zetterberg H, Sánchez-Juan P, Rodríguez-Rodríguez E. Early microglial and astrocyte reactivity in preclinical Alzheimer’s disease. Alzheimers Dement. 2025 Aug;21(8):e70502. doi: 10.1002/alz.70502. PMID: 40747577; PMCID: PMC12314543.
Link to article.