Affiliations: [a]
Non Invasive Brain Stimulation Unit/Department of Behavioural and Clinical Neurology, Santa Lucia Foundation IRCCS, Rome, Italy
| [b]
Stroke Unit, Department of Neuroscience, Tor Vergata Policlinic, Rome, Italy
| [c] Faculty of Sciences of Sport and Physical Education, Department of Physical Education, University of A Coruña, Pazos-Liáns, Oleiros, A Coruña, Spain
| [d] Neuroimaging Laboratory, Santa Lucia Foundation, IRCCS, Rome, Italy
Correspondence:
[*]
Correspondence to: Dr. Giacomo Koch, MD, PhD, Non Invasive Brain Stimulation Unit, Laboratorio di Neurologia Clinica e Comportamentale, IRCCS Fondazione S. Lucia, Via Ardeatina, 306- 00179-Rome, Italy. Tel.: +39 0651501181; E-mail: [email protected].
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.
