Researchers from the DeCo Research Chair, a joint initiative from CEU UCH and MICOF, Valencia’s pharmacists’ association, have studied the effect of type 2 diabetes medication on biomarkers for Alzheimer’s disease in cerebrospinal fluid. The research has been published in the Journal of Alzheimer’s Disease.
Researchers from the DeCo Research Chair, a joint initiative from the CEU Cardenal Herrera University (CEU UCH) and Valencia’s pharmacists’ association, the Muy Ilustre Colegio Oficial de Farmacéuticos de Valencia (MICOF), to support research into the early detection of cognitive impairment, have published a new study in the Journal of Alzheimer’s Disease. They examined the relationship between type 2 diabetes treatments and biomarkers for Alzheimer’s disease in cerebrospinal fluid. The study has been carried out in conjunction with members of the Alzheimer’s Disease Research Group at the Instituto de Investigación Sanitaria La Fe (IIS-La Fe) in Valencia and of the Center for Alzheimer Research at the Karolinka Institutet in Stockholm, Sweden.
This new study forms part of the doctoral research undertaken by Gemma García-Lluch, CEU UCH lecturer and researcher at the DeCo Research Chair. “We started from the hypothesis that insulin resistance is pivotal in mediating amyloid and tau dysregulations in Alzheimer’s disease,» said García-Lluch. «Amyloid fragments can accumulate and form plaques in the brain, and these are associated with Alzheimer’s disease. Tangles of tau protein can also form inside neurons, impairing their function. We decided to study patients with type 2 diabetes, focusing on the impact of different antidiabetic agents, daily dosage intake, and treatment duration on biomarkers for Alzheimer’s disease on cerebrospinal fluid.»
The study was undertaken on patients aged between 50 and 80 with type 2 diabetes with an Alzheimer’s disease diagnosis. These patients had been included between 2017 and 2023 in the VALCODIS (Valencian Cognitive Diseases Study) cohort of patients at the Neurology Unit of Valencia’s Hospital Universitario y Politécnico La Fe to facilitate the early diagnosis of this disease. “The biomarkers in cerebrospinal fluid studied in these patients were total tau (t-tau), phosphorylated tau 181 (p-tau), and amyloid-β 42 (Aβ42). We recorded the defined daily doses of antidiabetic prescriptions and the years of drug exposure duration at the time of the lumbar puncture for the sample of cerebrospinal fluid.»
The study has been carried out in conjunction with members of the Alzheimer’s Disease Research Group at the Instituto de Investigación Sanitaria La Fe (IIS-La Fe) in Valencia and of the Center for Alzheimer Research at the Karolinska Institute in Stockholm.
Three treatment types
One of the key findings was that the consumption of insulin was associated with a lower probability of abnormal Aβ42 levels and tau pathology. Diabetes type 2 patients treated with metformin were also less likely to suffer tau pathology when their diabetes was uncontrolled, but the drug also acted on t-tau and the relationship between t-tau and amyloid-β42 when it was administered with insulin and the patients’ diabetes was controlled. “This means that the combination of metformin and insulin may have protective effects on the brains of patients whose diabetes is well-managed,» she said. Lower probabilities of abnormal biomarker levels were also observed when other oral antidiabetic drugs were administered to metformin and insulin users. Treatment with inhibitors of sodium-glucose co-transporter 2 (iSGLT2) could reduce the risk of this pathology regardless of diabetes management.
Lucrecia Moreno, Professor of Pharmacology at CEU UCH and Director of the DeCo Research Chair, believes that “these results show the impact that antidiabetic treatment can have on pathological biomarkers related to Alzheimer’s disease. Therefore, treatments for this kind of diabetes in patients in whom Alzheimer’s is detected at an early stage could be adjusted, so that, together with other factors, we can slow the course of this neurodegenerative disease. We need to do more research of this type to assess the possible effects of chronic treatment on cognitive decline in older people”.
Research team
The team behind the study – “Associations between antidiabetic medications and cerebrospinal fluid biomarkers of Alzheimer’s disease”, published in the Journal of Alzheimer’s Disease – includes researchers from the DeCo-MICOF-CEU UCH Research Chair, Gemma García-Lluch, Mar García-Zamora, Lucrecia Moreno-Royo and Juan Pardo-Albiach; members of the Alzheimer’s Disease Research Group at the Instituto de Investigación Sanitaria La Fe (IIS-La Fe) in Valencia, Consuelo Cháfer, Miguel Baquero, Carmen Peña-Bautista, and Lourdes Álvarez; and staff from the Center for Alzheimer Research at the Karolinska Institutet in Stockholm (Sweden), Anna Marseglia and Eric Westman.
Members of three research groups will meet this week at CEU UCH, at the 3rd Interdisciplinary Conference on Raising Awareness of Cognitive Impairment, organized by the DeCo-MICOF-CEU UCH Research Chair. Sara García Ptacek, a neurologist and accredited researcher at Sweden’s Institutet Karolinska and Miquel Baquero Toledo, a neurologist and head of the Cognitive Disorders Unit will both be giving talks at the conference on 16th April. Mar García-Zamora, Gemma García-Lluch, María Gil, Gonzalo Adsuar, Cristina García and Amando Mengual, pre-doctoral DeCo reseachers and doctoral candidates at CEINDO (CEU’s international doctoral school), will also be reporting on their research at the event.
You can read “Associations between antidiabetic medications and cerebrospinal fluid biomarkers of Alzheimer’s disease”, in the Journal of Alzheimer’s Disease: https://doi.org/10.1177/13872877241304995
