Research reveals new properties for tau, a key protein in dementia
Researchers from King’s College London’s Institute of Psychiatry (IoP) have discovered that tau, a key constituent of the tangles present in the brain in Alzheimer’s disease, can be released from healthy neurons in the absence of cell death.
Alzheimer’s disease and other related dementias are known to be associated with changes in tau protein in the brain. This altered tau is thought to be asso-ciated with cell death, resulting in symptoms of dementia, such as memory loss.
However, the results, published today in EMBO Reports, suggest that release of tau is a normal process which is altered in the diseased brain. Importantly, the research shows that treatment of neurons with known biological signaling mole-cules increases the release of tau from the cell. The outflow of tau from neurons is therefore a physiological process that can be regulated by neuronal activity, offering a possible new approach in the hunt for novel therapeutic targets for the treatment of Alzheimer’s disease.
Dr Diane Hanger from the Department of Neuroscience at King’s IoP says: “Tau proteins help to support the shape of cells, but it looks likely that tau has other properties too. Our study shows that when cells are stimulated, tau is released from the cell. This is a normal process and not just the result of cells dying. It is possible that in the Alzheimer’s brain, when tau becomes altered, it could affect tau release from cells and perhaps also the spread of tau throughout the brain.”
Tau proteins stabilize microtubules, the long threads of polymers that help to maintain the structure of the cell. However, in Alzheimer’s disease and certain types of dementia, tau accumulates in nerve cells, where it contributes to neuro-degeneration.
In addition to aggregation within the cell, recent experiments have shown that tau is released from neuronal cells and taken up by neighbouring cells, allowing the spread of aggregated tau across the brain. This release could occur passively from dying neuronal cells, though some evidence suggests it might take place before neuronal cell death and neurodegeneration. Indeed, the new findings indicate that tau release is an active process in healthy neurons which could be altered in diseased brains.
In the study, Dr Amy Pooler, the lead author, also from King’s IoP, revealed that molecules such as potassium chloride, glutamate or an AMPA receptor agonist could release tau from cortical neurons in an active physiological process.
The new findings indicate that tau has previously unknown roles in biological signaling between cells, in addition to its well-established role in stabilizing microtubules.
Dr Hanger adds: “We believe that targeting the release of tau could be explored as a new therapeutic approach for the treatment of Alzheimer’s disease and oth-er dementias,”
The study was funded by The Henry Smith Charity, Alzheimer’s Research UK and The Wellcome Trust.
Image: Nerve cells are labelled for tau protein (green) and cell nuclei (blue). The amount of cell death (red) in cells exposed to (S)-AMPA is equivalent to that in untreated cells, indicating that tau release from (S)-AMPA-stimulated nerve cells is not due to cell death.
Paper reference: Pooler, A. et al. ‘Physiological release of endogenous tau is stimu-lated by neuronal activity', EMBO Reports doi: 10.1038/embor.2013.15
For further information, please contact Seil Collins, Press Officer, Institute of Psychiatry, King's College London. Email: seil.collins@kcl.ac.uk or tel: (+44) 0207 848 5377