A team of researchers at the Sant Pau Research Institute (IR Sant Pau) has demonstrated that the plasma biomarker p-tau217, obtained through a simple blood test, can predict the clinical progression of Alzheimer’s disease even in its earliest stages. This is when symptoms are not yet evident. The study, published in the journal Neurology, reinforces the role of blood tests in the future of diagnosing and monitoring dementias.
The study, conducted within the framework of the SPIN cohort (Sant Pau Initiative on Neurodegeneration), included 731 individuals with and without cognitive impairment who were followed for an average of up to 10 years. The researchers analyzed levels of p-tau217—a specific form of the tau protein associated with neurodegeneration—and observed that this marker not only correlates with the presence of Alzheimer’s disease but also enables prediction of the rate of cognitive decline and progression to more advanced stages of the disease. This includes dementia.
“This marker has enormous potential as a clinical tool. It not only accurately identifies Alzheimer’s disease, but also allows us to estimate how fast it will progress—an essential factor in making therapeutic decisions,” says Dr. Ignacio Illán, researcher in the Neurobiology of Dementia group and neurologist at Sant Pau Hospital, who led the study.
For her part, Judit Selma-González, first author and research neuropsychologist, also from the Neurobiology of Dementia group, highlights that “one of the most relevant findings is that p-tau217 allows us to identify people who do not yet have cognitive symptoms but are at higher risk of developing the disease in the short or medium term. This can help us better select patients eligible to participate in clinical trials of disease-modifying treatments.”
Until now, the most reliable biomarkers for detecting and monitoring Alzheimer’s disease have required invasive techniques such as lumbar puncture (to analyze cerebrospinal fluid) or costly procedures such as positron emission tomography (PET). The use of plasma p-tau217 offers a non-invasive, more accessible, and affordable alternative with both clinical and research applications.
The study indicated that p-tau217 levels increased progressively from the preclinical stages to the advanced stages of dementia, and were independently associated with a higher risk of cognitive decline (measured, among other tools, with the Mini-Mental State Examination) and conversion to dementia. In fact, the marker showed better prognostic ability than its cerebrospinal fluid equivalent, p-tau181, which is widely used today.
This advance is particularly relevant in the current context, where disease-modifying treatments—such as anti-amyloid antibodies—are already being approved, and their use depends on the stage of Alzheimer’s disease progression. The possibility of using a blood test to determine this clinical stage and monitor its progression represents a major step toward more personalized and precise medicine. “In a memory clinic, having access to this information through a blood test opens up possibilities that were previously limited to highly specialized centers,” notes Dr. Ignacio Illán.
This study was funded by the Instituto de Salud Carlos III (ISCIII) through projects PI14/01126, PI17/01019, PI18/00335, PI19/00882, PI18/00435, PI22/00611, INT19/00016, INT23/00048, PI17/01896, PI22/00307, PI20/01473, PI23/01786, PI21/00791, and PI24/00598, and co-funded by the European Union. It was also supported by research programs of the Spanish Biomedical Research Network Center on Neurodegenerative Diseases (CIBERNED) and the La Marató de 3cat Foundation (projects 20141210, 044412, and 20142610), as well as by the “la Caixa” Foundation (DABNI project), the Catalan Down Syndrome Foundation, the Víctor Grífols i Lucas Foundation, and the Government of Catalonia (2017-SGR-547, SLT006/17/125, SLT006/17/119, SLT002/16/408).
Several researchers were supported by competitive contracts, including Río Hortega and Sara Borrell fellowships from ISCIII in collaboration with the European Social Fund Plus. In addition, various authors are affiliated with the Global Brain Health Institute (GBHI) as fellows of the Atlantic Fellow for Equity in Brain Health program, with additional funding from the Alzheimer’s Association, the Alzheimer Society, and the Jérôme Lejeune Foundation. International collaboration was strengthened through the participation of the Institute of Neuroscience and Physiology at the University of Gothenburg (Sweden), the Banner Alzheimer’s Institute (United States), and the Barcelona Down Medical Center.
Selma-Gonzalez J, Rubio-Guerra S, García-Castro J, Vera-Campuzano E, Sala I, Sánchez-Saudinós MB, Zhu N, Arranz J, Arriola-Infante JE, Rodríguez-Baz Í, Maure-Blesa L, Dols-Icardo O, Videla L, Valldeneu S, Barroeta I, Santos-Santos M, Carmona-Iragui M, Vaqué-Alcázar L, Alvarez-Sanchez E, Lorente O, Carreras M, Belbin O, Arslan B, Ashton NJ, Zetterberg H, Blennow K, Montoliu-Gaya L, Bejanin A, Lleó A, Fortea J, Alcolea D, Illan-Gala I. Association of plasma phosphorylated tau 217 with clinical deterioration across Alzheimer disease stages. Neurology. 2025;105:e213769. https://doi.org/10.1212/WNL.0000000000213769.
