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Scientific result | Alzheimer's disease | Molecular mechanisms
Neurofibrillary tangles are large aggregates of tau protein found in the neurons of people with Alzheimer's disease. Historically, they have been thought to be at least partially responsible for the pathology. However, the results of a study performed by researchers at MIRCen (François Jacob Institute of Biology/CEA) suggest to the contrary that neurofibrillary tangles may be protective.
Alzheimer's disease is the leading cause of neurological disability. It manifests as a progressive and irreversible loss of cognitive functions, particularly memory. Histopathologically, Alzheimer's disease is characterized by the hyperphosphorylation1 of the tau protein and its aggregation in different types of cells. Neurofibrillary degeneration is largely defined by the presence of very dense intracellular tau aggregates called neurofibrillary tangles (NFTs). These latter have been long thought to be a cause of the neurodegeneration seen in patients: indeed their number is strongly correlated with neuronal death and cognitive decline. However, neuronal death and NFTs do not occur in the same zones of the patient's brain. Furthermore, studies performed in transgenic mice have shown that neurons developing NFTs survive and even communicate with one another. Thus, researchers have hypothesized that complex, soluble forms (or "species") of tau with an intermediate level of aggregation (oligomeric forms) may be more toxic than NFTs.
The results of the study suggest that in vivo, NFTs may cause neurons no harm, at least in the short term, whereas soluble tau species, probably oligomers, appear to be toxic. They furthermore imply that the level of tau hyperphosphorylation may be a more pertinent method of assessing neurodegeneration than NFT count, which only imperfectly reflects disease severity. "Our study suggests that it is surely more appropriate to develop imaging tracers and therapeutic agents targeting specifically these soluble tau species instead of NFTs," concludes Ms. Cambon.
Potentiating tangle formation reduces acute toxicity of soluble Tau species in rat | Brain
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