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Decades before the first symptoms of Alzheimer's disease appear, some changes associated with the disease may begin to leave a trace in the blood. A study by the Sant Pau Research Institute (IR Sant Pau) has found that, in people with Down syndrome, levels of β-synuclein, a protein related to synaptic function, begin to rise in the third decade of life, long before symptoms appear and earlier than other blood biomarkers of Alzheimer's disease.

The results, published in Alzheimer's & Dementia, stem from a collaboration between Sant Pau Hospital in Barcelona, Martin Luther University in Germany and the German Center for Neurodegenerative Diseases. They position β-synuclein as a promising marker of the earliest synaptic changes associated with the disease.

According to estimates based on participants' ages, β-synuclein levels begin to differ from those observed in people without Down syndrome approximately 21 years before the average age at diagnosis of prodromal Alzheimer's disease in the cohort studied.

"One of the major challenges in Alzheimer's research is understanding what is happening in the brain many years before the first symptoms appear. Gaining a more in-depth understanding of these earliest changes is essential to identifying when synapses begin to fail and to opening the door to studying interventions at increasingly early stages of the disease," explains Dr. Olivia Belbin, head of the Molecular Neurodegeneration group at IR Sant Pau and corresponding author of the study.

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