Cerebrospinal fluid tau levels indicate aberrant neuronal plasticity in Alzheimer disease
Pieter Jelle Visser,
Lianne M. Reus,
Frans RJ Verhey,
José Luís Molinuevo,
Stephanie J.B. Vos,
August B Smit,
Charlotte E. Teunissen,
Betty M. Tijms
Posted 03 Nov 2020
medRxiv DOI: 10.1101/2020.10.29.20211920
Posted 03 Nov 2020
Alzheimers 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.
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