Cerebrospinal fluid total tau levels indicate aberrant neuronal plasticity in Alzheimer's disease

Pieter Jelle Visser, Lianne M Reus, Johan Gobom, Iris Jansen, Ellen Dicks, Magda Tsolaki, Frans R J Verhey, Julius Popp, Pablo Martinez-Lage, Rik Vandenberghe, Alberto Lleó, José Luís Molinuevo, Sebastiaan Engelborghs, Yvonne Freund-Levi, Lutz Froelich, Kristel Sleegers, Valerija Dobricic, Shengjun Hong, Simon Lovestone, Johannes StrefferStephanie J B Vos, Isabelle Bos, August B Smit, Kaj Blennow, Philip Scheltens, Charlotte E Teunissen, Lars Bertram, Henrik Zetterberg, Betty M Tijms

Onderzoeksoutput: Preprintpeer review

Samenvatting

Alzheimer's disease (AD) is characterised by abnormal amyloid beta and tau processing. Previous studies reported that cerebrospinal fluid (CSF) total tau (t-tau) levels vary between patients. Here we show that CSF t-tau variability is associated with distinct impairments in neuronal plasticity mediated by gene repression factors SUZ12 and REST. AD individuals with abnormal t-tau levels have increased CSF concentrations of plasticity proteins regulated by SUZ12 and REST. AD individuals with normal t-tau, on the contrary, have decreased concentrations of these plasticity proteins and increased concentrations in proteins associated with blood-brain and blood CSF-barrier dysfunction. Genomic analyses suggested that t-tau levels in part depend on genes involved in gene expression. The distinct plasticity abnormalities in AD as signaled by t-tau urge the need for personalised treatment.

Originele taal-2English
Aantal pagina's47
DOI's
StatusUnpublished - nov 2020

Publicatie series

NaammedRxiv : the preprint server for health sciences

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