TY - JOUR
T1 - Cerebrospinal fluid total tau levels indicate aberrant neuronal plasticity in Alzheimer's disease
AU - Visser, Pieter Jelle
AU - Reus, Lianne Maria
AU - Gobom, Johan
AU - Jansen, Iris
AU - Dicks, Ellen
AU - Tsolaki, Magda
AU - Verhey, Frans R J
AU - Popp, Julius
AU - Martinez-Lage, Pablo
AU - Vandenberghe, Rik
AU - Lleó, Alberto
AU - Molinuevo, José Luís
AU - Engelborghs, Sebastiaan
AU - Freund-Levi, Yvonne
AU - Froelich, Lutz
AU - Sleegers, Kristel
AU - Dobricic, Valerija
AU - Hong, Shengjun
AU - Lovestone, Simon
AU - Streffer, Johannes
AU - Vos, Stephanie J B
AU - Bos, Isabelle
AU - Smit, August B
AU - Blennow, Kaj
AU - Scheltens, Philip
AU - Teunissen, Charlotte E
AU - Bertram, Lars
AU - Zetterberg, Henrik
AU - Tijms, Betty M
PY - 2020/11/3
Y1 - 2020/11/3
N2 - 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.
AB - 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.
U2 - https://doi.org/10.1101/2020.10.29.20211920
DO - https://doi.org/10.1101/2020.10.29.20211920
M3 - Article
C2 - 33173883
JO - MedRxIv
JF - MedRxIv
ER -