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The aged population has a reduced ability to form and recall new memories, and this faculty is further impaired in individuals suffering from diseases of aging such as tauopathies. These are 16 neurodegenerative disorders that present aggregation of the microtubule-associated protein tau inside brain cells. The most common tauopathy is Alzheimer’s disease (AD), which is characterized by progressive memory loss. Nascent protein production, which is essential for memory formation, is attenuated in aging and AD brains. Replenishment of synaptic proteins is necessary for neuronal signaling, cell survival, and structural integrity, among others. Therefore, reduced translation efficiency likely contributes to memory decline in aging and AD. Ribosomes are the hub of RNA translation. They are composed of ribosomal RNA and 80 ribosome-binding proteins such as S6. Once transcribed, mRNA exits the nucleus and is translated in perinuclear ribosomes. However, due to the elongated neuronal morphology, RNA translation also takes place distally from the nucleus. Ribosomes and mRNA are transported along microtubules, where they form complexes with proteins such as tau. However, the specific ribosomal protein to which tau anchors ribosomes is unknown, and the implications of this interaction for aging and diseases are also unspecified. We recently identified that tau associates with ribosomal proteins (Fig. 1) and specifically with S6 (Fig. 2). Interestingly, S6 showed greater affinity to two pathological tau variants (Fig. 3). These data suggest that there are normal and pathological effects of tau binding to the ribosome. The functional consequence of the tau-S6 interaction in the aging and Alzheimer’s brains is unknown. Since S6 regulates translation of all elongation and some initiation factors, we hypothesize that phospho-tau, which is increased in an age- and AD-dependent manner, downregulates S6 function and overall ribosomal translation efficiency.
Effective start/end date2/1/151/31/17


  • Alzheimers Association: $100,000.00


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