Biomarker helps to diagnose Alzheimer's early
European researchers have found new forms of tau protein that become abnormal in the very early stages of Alzheimer’s disease (AD) before cognitive problems develop, and created new tools to detect these subtle changes in human samples. The team’s research could enable the detection of Alzheimer’s much earlier than current approaches, as well as the testing of therapies against this devastating disease.
Alzheimer’s disease is characterised by two pathological changes in brain tissue: one is a protein called tau while the other involves the amyloid-beta peptide. Both can form clumps of aggregates that progressively accumulate in specific areas of the brain. For tau, individual units of the protein can aggregate into finely ordered fibrillar structures facilitated by a biochemical process called phosphorylation.
Throughout the disease process, amyloid beta and phosphorylated tau (p-tau) are released from the brain into the cerebrospinal fluid; the released proteins are used as reliable surrogate markers for clinical diagnoses of Alzheimer’s disease. But amyloid-beta levels in the cerebrospinal fluid become abnormal several years before p-tau, with current clinical tests for p-tau only becoming abnormal when memory failings develop. This makes it difficult to identify people with very early-stage Alzheimer’s, before it is too late.
Scientists from the University of Gothenburg, together with their colleagues at the Barcelonaßeta Research Centre (BBRC), the Ljubljana University Medical Centre and the University of Paris, have now discovered that there are specific forms of p-tau that undergo very minute increases in cerebrospinal fluid and blood in people with emerging Alzheimer pathology. Consequently, the researchers developed highly sensitive techniques to measure these biological markers that precede clinical signs by several years.
In the first study, conducted in at the BBRC, about one-third of the 381 people evaluated had brain evidence of Alzheimer’s pathology but without any cognitive problems, meaning that these changes could not be detected in the clinic by memory assessments. The new p-tau markers correctly identified these emerging abnormalities measured in cerebrospinal fluid and regular blood samples.
Subsequent studies performed in Gothenburg, Paris and Ljubljana revealed that these new markers continue to increase from the preclinical stage through the onset of cognitive problems to the late dementia stages. For this reason, progressive increases in p-tau could provide insights into the biological and clinical development of Alzheimer’s disease. The studies have been published in EMBO Molecular Medicine and Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
“The remarkable findings reported in these publications show that the new highly sensitive tools capture the earliest Alzheimer disease changes in the brain in clinically normal people,” said Dr Thomas Karikari from the University of Gothenburg, who co-led the discovery. “These tools therefore have the potential to advance population screening and clinical trials.”
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