Reversal of LTP-Like Cortical Plasticity in Alzheimer's Disease Patients with Tau-Related Faster Clinical Progression

Giacomo Koch, Francesco Di Lorenzo, Miguel Fernandez Del Olmo, Sonia Bonní, Viviana Ponzo, Carlo Caltagirone, Marco Bozzali, Alessandro Martorana

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)605-16
Number of pages12
JournalJournal of Alzheimer's Disease
Issue number2
Publication statusPublished - 2016


  • Aged
  • Alzheimer Disease
  • Amyloid beta-Peptides
  • Cognition
  • Disease Progression
  • Evoked Potentials, Motor
  • Female
  • Humans
  • Male
  • Motor Cortex
  • Neuronal Plasticity
  • Neuropsychological Tests
  • Phosphorylation
  • Transcranial Magnetic Stimulation
  • tau Proteins
  • Journal Article
  • Research Support, Non-U.S. Gov't


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