%0 Journal Article %J J Alzheimers Dis %D 2016 %T Reversal of LTP-Like Cortical Plasticity in Alzheimer's Disease Patients with Tau-Related Faster Clinical Progression. %A Koch, Giacomo %A Di Lorenzo, Francesco %A Del Olmo, Miguel Fernandez %A Bonní, Sonia %A Ponzo, Viviana %A Caltagirone, Carlo %A Bozzali, Marco %A Martorana, Alessandro %K Aged %K Alzheimer Disease %K Amyloid beta-Peptides %K Cognition %K Disease Progression %K Evoked Potentials, Motor %K Female %K Humans %K Male %K Motor Cortex %K Neuronal Plasticity %K Neuropsychological Tests %K Phosphorylation %K tau Proteins %K Transcranial Magnetic Stimulation %X

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.

%B J Alzheimers Dis %V 50 %P 605-16 %8 2016 %G eng %N 2 %1 http://www.ncbi.nlm.nih.gov/pubmed/26757193?dopt=Abstract %R 10.3233/JAD-150813