Good news, but older news!
"... Researchers ... recently introduced new genetically modified mouse models that express humanized versions of MAPT, a gene known to encode the tau protein. Using these models ... the researchers gathered new insight suggesting that an alteration known as tau hyperphosphorylation plays a key role in the early stages of tau pathology. ..."
From the abstract:
"Tau pathology is a hallmark of several neurodegenerative diseases, including frontotemporal dementia and Alzheimer’s disease. However, the sequence of events and the form of tau that confers toxicity are still unclear, due in large part to the lack of physiological models of tauopathy initiation and progression in which to test hypotheses.
We have developed a series of targeted mice expressing frontotemporal-dementia-causing mutations in the humanized MAPT gene to investigate the earliest stages of tauopathy. MAPTInt10+3G>A and MAPTS305N;Int10+3G>A lines show abundant hyperphosphorylated tau in the hippocampus and entorhinal cortex, but they do not develop seed-competent fibrillar structures.
Accumulation of hyperphosphorylated tau was accompanied by neurite degeneration, loss of viable synapses and indicators of behavioral abnormalities. Our results demonstrate that neuronal toxicity can occur in the absence of fibrillar, higher-order structures and that tau hyperphosphorylation is probably involved in the earliest etiological events in tauopathies showing isoform ratio imbalance."
In vivo hyperphosphorylation of tau is associated with synaptic loss and behavioral abnormalities in the absence of tau seeds (open access)
Fig. 3: Map of pathological tau detected by AT8 antibody staining in MAPTInt10+3 and MAPTS305N;Int10+3 mice.
Fig. 7: Memory deficits indicated in MAPTS305N;Int10+3 KI mice.
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