Summary: Researchers confirm that both amyloid beta and tau proteins are present together in brain regions tied to memory and information processing during the very early stages of Alzheimer’s disease.
Source: University of Aberdeen.
University of Aberdeen researchers identify early co-occurrence of amyloid beta and tau in memory-related brain regions
Researchers at the University of Aberdeen report that two molecules long implicated in Alzheimer’s disease—amyloid beta (Aβ) and tau—are detectable together in the same brain region at very early stages of the illness. The discovery narrows the gap in understanding how these proteins relate to disease onset and progression, and it may influence the design of future diagnostics and drug development strategies for Alzheimer’s disease.
The study, supported by Alzheimer’s Research UK, analysed post-mortem human brain tissue made available through the Brains for Dementia Research platform. The investigative team, led by Dr David Koss and Professor Bettina Platt, developed sensitive laboratory methods to evaluate different forms of tau and Aβ and to determine how each contributes to the initial phases and advancement of Alzheimer’s.
What the study found
Using improved biochemical assays and tissue-profiling techniques, the researchers examined lateral temporal lobe samples (Brodmann area 21) from a series of human cases spanning non-demented to clinical Alzheimer’s disease. They detected elevated levels of phosphorylated tau, pathological tau conformations and oligomeric tau species, alongside increased soluble forms of Aβ. These soluble forms of tau and Aβ were measurable earlier than previously reported fibrillar changes, and they were present together in the same brain region associated with memory and information processing.
The team’s evidence indicates a close relationship between soluble tau and soluble Aβ in the early disease stages. Multiple tau markers and total soluble Aβ correlated with established Braak staging and with cognitive measures, suggesting these soluble species track with cognitive decline and disease progression. Some previously reported Aβ oligomers were not consistently observed and may reflect technical variability rather than reliable pathology.
Implications for diagnosis and drug discovery
Professor Bettina Platt explained that the field has long debated whether tau or amyloid is the primary driver of neuronal damage in Alzheimer’s. “These two suspects have rarely been shown together in human cases at an early stage, and their relationship has been unclear,” she said. The present findings bridge conflicting reports from earlier studies and support the idea that tau and amyloid interact early in the disease process.
Dr David Koss added that early identification of Alzheimer’s is a major scientific challenge. He noted that the new results could help guide future work to develop more sensitive diagnostic methods and to prioritise biochemical targets for therapeutic intervention. “These early-stage changes in the brains of people with Alzheimer’s disease highlight key biochemical processes that may not only enable improved diagnostic procedures but may also inform drug development programs,” he said.
Dr Rosa Sancho, Head of Research at Alzheimer’s Research UK, emphasized that the study helps clarify when and where specific forms of the hallmark proteins first appear. She noted that tau and Aβ build-ups in plaques and tangles do not always align well with neuronal damage, and that recognising which soluble species drive early Alzheimer’s could allow scientists to design drugs that target those precise forms and to develop more accurate diagnostic tools.
Funding: This research was funded by Alzheimer’s Research UK.
Source: Wendy Skene, University of Aberdeen.
Original research: The findings are reported in the paper titled “Soluble pre-fibrillar tau and β-amyloid species emerge in early human Alzheimer’s disease and track disease progression and cognitive decline,” authored by David J. Koss, Glynn Jones, Anna Cranston, Heidi Gardner, Nicholas M. Kanaan and Bettina Platt, and published in Acta Neuropathologica. The study provides open-access details of methods and results that underpin the conclusions about soluble tau and Aβ species in early Alzheimer’s.
Post-mortem studies of Alzheimer’s disease have produced mixed evidence about how β-amyloid aggregates and tau neurofibrillary tangles relate to clinical dementia. Recent attention has focused on soluble, pre-fibrillar forms of tau and Aβ as potentially toxic species relevant to disease onset. In this study, lateral temporal lobe tissue from 46 human cases was profiled using Western blot and native state dot blot assays to quantify phospho-tau, pathological tau conformations, oligomeric tau and soluble Aβ species. Elevations in multiple tau markers and in soluble Aβ forms were associated with medical diagnosis and Braak stage, and these soluble species correlated with cognitive decline measures. The results indicate that soluble tau and Aβ co-localise early in Alzheimer’s and have strong links to disease progression and cognitive impairment, supporting a revised view of early disease biology that emphasises soluble protein species over later fibrillar deposits.
If you are following research or clinical developments in Alzheimer’s disease, these findings underscore the importance of targeting specific soluble forms of tau and amyloid beta in early diagnostic and therapeutic strategies. The data contribute to a growing body of evidence that early biochemical changes precede classic plaque and tangle pathology and are closely tied to cognitive decline.