Summary: Researchers confirm both amyloid beta and tau are present in brain areas associated with memory and information processing during very early stages of Alzheimer’s.
Source: University of Aberdeen.
Researchers from the University of Aberdeen have detected key changes in the brains of people with Alzheimer’s disease.
The study confirmed for the first time that two molecules assumed to contribute to the disease process are both present at very early stages of Alzheimer’s in an area of the brain that is involved in memory formation and information processing.
This research, funded by Alzheimer’s Research UK, will have implications for the development of new drugs, but may also provide important information for diagnosis of the disease and in the post-mortem pathology of tissues.
The team, led by Dr David Koss and Professor Bettina Platt, used human brain samples provided by the ‘Brains for Dementia Research’ platform to investigate changes in the brain at different stages of Alzheimer’s disease.
Specifically, the researchers developed novel ways to study two proteins (tau and amyloid), both associated with Alzheimer’s disease, and determined how each one contributed to the onset, progression and symptoms of the disease.
Previous research had suggested that the two proteins initially emerge in separate brain regions but these results published in the journal Acta Neuropathologica show for the first time that both proteins are present in the very early stages of the disease in the same brain region, which suggests that they both contribute to the disease process and are more connected than previously recognised.
Professor Bettina Platt said: “In the field of Alzheimer’s and dementia research there has been a long-running battle regarding the two main suspects that might cause brain cells to die – tau and amyloid. These two have never been brought together in human cases, and the relationship between them has not been clear. Our observations therefore consolidate conflicting evidence from other studies on the role of the proteins in the disease process and strongly support a notion of an early stage interaction between the two.
“It has long been assumed that Alzheimer’s-related changes within the brain occur long before symptoms are evident, but so far reliable methods to detect these were elusive. However, we have managed to modify experimental procedures in a way that we can now very sensitively determine when and where these proteins appear, and the big surprise was that they both appear together very early on, and in the same brain area. In doing so we have established a new benchmark for pathological investigations.
“Therefore, a long-standing puzzle in the field of dementia research has now been resolved to a large extent.”
Dr Koss added: “The entire research community is in agreement that it is a primary challenge to identify Alzheimer’s disease early – and our findings will go some way to help achieve this, though ultimately it will be up to the scientific community to further evaluate and build upon these results.
“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.”
Dr Rosa Sancho, Head of Research at Alzheimer’s Research UK, said: “This new study describes in detail the early appearance of both key hallmark Alzheimer’s proteins – tau and amyloid, previously thought to appear at different stages of Alzheimer’s disease. These proteins have long-puzzled scientists, as although we know that amyloid and tau make up the plaques and tangles found in the brains of people with Alzheimer’s, these build-ups don’t always correlate well with damage occurring to nerve cells.
“This study shows that specific forms of tau and amyloid appear early in the disease process in the same brain region, before plaques and tangles are formed. Understanding which forms of tau and amyloid drive the early stages of Alzheimer’s will allow scientists to design drugs to target these specific forms and find new ways to accurately diagnose people.”
About this neurology research article
Funding: This new research was funded by Alzheimer’s Research UK.
Source: Wendy Skene – University of Aberdeen Image Source: This NeuroscienceNews.com image is adapted from the University of Aberdeen press release. Original Research: Full open access research for “Soluble pre-fibrillar tau and β-amyloid species emerge in early human Alzheimer’s disease and track disease progression and cognitive decline” by David J. Koss, Glynn Jones, Anna Cranston, Heidi Gardner, Nicholas M. Kanaan, and Bettina Platt in Acta Neuropathologica. Published online October 21 2016 doi:10.1007/s00401-016-1632-3
Cite This NeuroscienceNews.com Article
[cbtabs][cbtab title=”MLA”]University of Aberdeen. “Early Signs of Alzheimer’s Identified.” NeuroscienceNews. NeuroscienceNews, 1 December 2016. <https://neurosciencenews.com/alzheimers-early-signs-5692/>.[/cbtab][cbtab title=”APA”]University of Aberdeen. (2016, December 1). Early Signs of Alzheimer’s Identified. NeuroscienceNews. Retrieved December 1, 2016 from https://neurosciencenews.com/alzheimers-early-signs-5692/[/cbtab][cbtab title=”Chicago”]University of Aberdeen. “Early Signs of Alzheimer’s Identified.” https://neurosciencenews.com/alzheimers-early-signs-5692/ (accessed December 1, 2016).[/cbtab][/cbtabs]
Soluble pre-fibrillar tau and β-amyloid species emerge in early human Alzheimer’s disease and track disease progression and cognitive decline
Post-mortem investigations of human Alzheimer’s disease (AD) have largely failed to provide unequivocal evidence in support of the original amyloid cascade hypothesis, which postulated deposition of β-amyloid (Aβ) aggregates to be the cause of a demented state as well as inductive to tau neurofibrillary tangles (NFTs). Conflicting evidence suggests, however, that Aβ plaques and NFTs, albeit to a lesser extent, are present in a substantial subset of non-demented individuals. Hence, a range of soluble tau and Aβ species has more recently been implicated as the disease-relevant toxic entities. Despite the incorporation of soluble proteins into a revised amyloid cascade hypothesis, a detailed characterization of these species in the context of human AD onset, progression and cognitive decline has been lacking. Here, lateral temporal lobe samples (Brodmann area 21) of 46 human cases were profiled via tau and Aβ Western blot and native state dot blot protocols. Elevations in phospho-tau (antibodies: CP13, AT8 and PHF-1), pathological tau conformations (MC-1) and oligomeric tau (TOC1) agreed with medical diagnosis (non-AD cf. AD) and Braak stage classification (low, intermediate and high), alongside elevations in soluble Aβ species (MOAB-2 and pyro-glu Aβ) and a decline in levels of the amyloid precursor protein. Strong correlations were observed between individual Braak stages and multiple cognitive measures with all tau markers as well as total soluble Aβ. In contrast to previous reports, SDS-stable Aβ oligomers (*56) were not found to be reliable for all classifications and appeared likely to be a technical artefact. Critically, the robust predictive value of total soluble Aβ was dependent on native state quantification. Elevations in tau and Aβ within soluble fractions (Braak stage 2–3 cf. 0) were evident earlier than previously established in fibril-focused disease progression scales. Together, these data provide strong evidence that soluble forms of tau and Aβ co-localise early in AD and are closely linked to disease progression and cognitive decline.
“Soluble pre-fibrillar tau and β-amyloid species emerge in early human Alzheimer’s disease and track disease progression and cognitive decline” by David J. Koss, Glynn Jones, Anna Cranston, Heidi Gardner, Nicholas M. Kanaan, and Bettina Platt in Acta Neuropathologica. Published online October 21 2016 doi:10.1007/s00401-016-1632-3