Cerebrospinal fluid total tau levels indicate aberrant neuronal plasticity in Alzheimer's disease.
Pieter Jelle VisserLianne M ReusJohan GobomIris JansenEllen DicksMagda TsolakiFrans R J VerheyJulius PoppPablo Martinez-LageRik VandenbergheAlberto LleóJosé Luís MolinuevoSebastiaan EngelborghsYvonne Freund-LeviLutz FroelichKristel SleegersValerija DobricicShengjun HongSimon LovestoneJohannes StrefferStephanie J B VosIsabelle BosAugust B SmitKaj BlennowPhilip ScheltensCharlotte E TeunissenLars BertramHenrik ZetterbergBetty M TijmsPublished in: medRxiv : the preprint server for health sciences (2020)
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.