In Alzheimer's disease and other 'Tauopathies' the Tau protein (which normally controls the polymerization of microtubules) becomes hyperphosphorylated and self-aggregates into insoluble fibrils called 'neurofibrillary tangles' within neurons. Excessive phosphorylation of Tau by a kinase called GSK3 is implicated in neurofibrillary tangle formation and neuron death in Alzheimer's disease. The Spanish biochemists Felix Hernandez and Jesus Avila made seminal discoveries concerning Tau tangle chemistry. In this episode I talk with Felix about that work and its importance for understanding, preventing, and treating Tauopathies. Interestingly, lithium (the third element on the periodic table) has long been known to be an effective treatment for bipolar disorder and more than 20 years ago Felix and his colleagues showed that lithium treatment prevents tau hyperphosphorylation and neurofibrillary tangle formation in a mouse model of frontotemporal dementia. Very recent findings from another laboratory suggest that low levels of lithium in the brain may be a risk factor for Alzheimer's disease. Clinical trials of lithium for tauopathy patients in the early stages of the disease are in progress.

LINKS

Felix and Jesus laboratory website:

https://www.cbm.uam.es/index.php/scientific-programs/physiological-and-pathological-processes/molecular-neuropathology/tau-function-and-dysfunction-in-alzheimer-disease/

Key articles

https://pmc.ncbi.nlm.nih.gov/articles/PMC140191/pdf/cde013.pdf

https://pubmed.ncbi.nlm.nih.gov/17059563/

https://pubmed.ncbi.nlm.nih.gov/14624025/

https://pubmed.ncbi.nlm.nih.gov/40770094/