title: Reversal of LTP-Like Cortical Plasticity in Alzheimer's Disease Patients with Tau-Related Faster Clinical Progression.
abstract: Cerebrospinal fluid (CSF) concentrations of amyloid-β (Aβ), total tau (t-tau), and phosphorylated tau proteins are associated with different clinical progression in Alzheimer's disease (AD). We enrolled forty newly diagnosed AD patients, who underwent lumbar puncture, and carried out a K-means cluster analysis based on CSF biomarkers levels, resulting in two AD patient groups: Cluster 1 showed relatively high levels of Aβ and low levels of tau; Cluster 2 showed relatively low levels of Aβ and high levels of tau. Cortical plasticity was tested using the intermittent and continuous theta burst stimulation (iTBS and cTBS) protocols evoking respectively long-term potentiation (LTP) and depression (LTD). Cholinergic transmission was tested by the short-latency afferent inhibition protocol. Neurophysiological evaluation showed that the two AD groups differed in terms of cortical plasticity: after iTBS, Cluster 2 patients showed a remarkable reversal of LTP toward LTD that was not observed in Cluster 1. LTD and central cholinergic transmission did not differ between groups. Patients were assessed longitudinally with Mini-Mental State Examination at 6, 12, and 18 month follow-ups. Cluster 2 AD had a faster cognitive decline already evident at the 12 month follow-up. High tau CSF levels were associated with LTD-like cortical plasticity and faster clinical progression. These results suggest that more aggressive tau pathology is associated with prominent LTD-like mechanisms of cortical plasticity and faster cognitive decline.
authors.affiliation: Non Invasive Brain Stimulation Unit/Department of Behavioural and Clinical Neurology, Santa Lucia Foundation IRCCS, Rome, Italy.|Stroke Unit, Department of Neuroscience, Tor Vergata Policlinic, Rome, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Koch
authors.affiliation: Non Invasive Brain Stimulation Unit/Department of Behavioural and Clinical Neurology, Santa Lucia Foundation IRCCS, Rome, Italy.|Stroke Unit, Department of Neuroscience, Tor Vergata Policlinic, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Lorenzo
authors.affiliation: Faculty of Sciences of Sport and Physical Education, Department of Physical Education, University of A Coruña, Pazos-Liáns, Oleiros, A Coruña, Spain.
authors.forename: Miguel Fernandez
authors.initials: MF
authors.lastname: Del Olmo
authors.affiliation: Non Invasive Brain Stimulation Unit/Department of Behavioural and Clinical Neurology, Santa Lucia Foundation IRCCS, Rome, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Bonní
authors.affiliation: Non Invasive Brain Stimulation Unit/Department of Behavioural and Clinical Neurology, Santa Lucia Foundation IRCCS, Rome, Italy.
authors.forename: Viviana
authors.initials: V
authors.lastname: Ponzo
authors.affiliation: Non Invasive Brain Stimulation Unit/Department of Behavioural and Clinical Neurology, Santa Lucia Foundation IRCCS, Rome, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Caltagirone
authors.affiliation: Neuroimaging Laboratory, Santa Lucia Foundation, IRCCS, Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Bozzali
authors.affiliation: Stroke Unit, Department of Neuroscience, Tor Vergata Policlinic, Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Martorana
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D003071:Cognition / Q000502:physiology*; D018450:Disease Progression; D019054:Evoked Potentials, Motor / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D009044:Motor Cortex / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000502:physiology*; D009483:Neuropsychological Tests; D010766:Phosphorylation; D050781:Transcranial Magnetic Stimulation; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D016875:tau Proteins
keywords: Alzheimer’s disease; amyloid-beta; cortical plasticity; long-term depression; long-term potentiation; tau; transcranial magnetic stimulation