SORLA protein shields brain from Alzheimer's tau damage
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Researchers at Sanford Burnham Prebys have identified a natural brain protein, SORLA, that protects against toxic tau tangles linked to Alzheimer's disease. In mice, extra SORLA reduced tau accumulation, brain atrophy, and neuronal damage, while its absence worsened pathology. The findings, published July 17 in Science Advances, suggest a potential drug target for tau-related dementias.
Tau Tangles and Neurodegeneration
Tau protein normally stabilizes microtubules in neurons. In Alzheimer's and other tauopathies, tau forms toxic tangles that disrupt brain circuits and cause cognitive decline. The study focused on SORLA, a protein previously known to suppress amyloid-beta accumulation, another Alzheimer's hallmark. Timothy Huang, PhD, noted that little was known about SORLA's effect on tau tangles.
Mouse Model Findings
Researchers crossbred mice with elevated human SORLA with mice prone to tau tangles and brain atrophy. Higher SORLA levels reduced tau hyperphosphorylation, a key step in tangle formation. The protein also decreased tau accumulation, brain atrophy, and preserved neuronal connections. Mice lacking SORLA experienced more severe damage.
Therapeutic Implications
The study identifies SORLA as a natural defense mechanism against tau pathology. The findings raise the possibility of developing therapies that boost SORLA activity or mimic its function. This could offer a new approach for Alzheimer's and other tau-related dementias, though human trials remain years away.
What's Next
Further studies will explore SORLA's mechanism and test potential drug candidates in animal models. It remains unclear whether boosting SORLA in humans will be safe or effective against tau pathology.
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SORLA protein shields brain from Alzheimer's tau damage
