Association between plasma phospho-tau181 and cognitive change from age 73 to 82: Lothian Birth Cohort 1936

Saunders, T. S.; Heslegrave, A.; King, D.; Harris, S.; Ritchie, C. W.; Muniz-Terrera, G.; Deary, I. J.; Cox, S. R.; Zetterberg, H.; Spires-Jones, T.

doi:10.1101/2021.11.24.469836

bioRxiv · 10.1101/2021.11.24.469836

Association between plasma phospho-tau181 and cognitive change from age 73 to 82: Lothian Birth Cohort 1936

Saunders, T. S.·Heslegrave, A.·King, D.·Harris, S.·Ritchie, C. W.·Muniz-Terrera, G.·Deary, I. J.·Cox, S. R.·Zetterberg, H.·Spires-Jones, T.

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Abstract

INTRODUCTIONPlasma phospho-tau 181 (p-tau181) is a promising blood biomarker for Alzheimers disease. However, its predictive validity for age-related cognitive decline without dementia remains unclear. Several forms of p-tau have been shown to contribute to synapse degeneration, but it is unknown whether p-tau181 is present in synapses. Here, we tested whether plasma p-tau181predicts cognitive decline and whether it is present in synapses in human brain. METHODSGeneral cognitive ability and plasma p-tau181 concentration were measured in 195 participants at ages 72 and 82. Levels of p-tau181 in total homogenate and synaptic fractions were compared with western blot (n=10-12 per group), and synaptic localisation was examined using array tomography. RESULTSElevated baseline plasma p-tau181 and increasing p-tau181 over time predicted steeper general cognitive decline. We observe p-tau181 in neurites, presynapses, and post-synapses in the brain. DISCUSSIONBaseline and subsequent change in plasma p-tau181 may represent rare biomarkers of differences in cognitive ageing across the 8th decade of life and may play a role in synaptic function in the brain.

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Saunders, T. S., Heslegrave, A., King, D., Harris, S., Ritchie, C. W., Muniz-Terrera, G., Deary, I. J., Cox, S. R., Zetterberg, H., Spires-Jones, T.. 2021-11-25. Association between plasma phospho-tau181 and cognitive change from age 73 to 82: Lothian Birth Cohort 1936. https://doi.org/10.1101/2021.11.24.469836

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