Title | Reversal of LTP-Like Cortical Plasticity in Alzheimer's Disease Patients with Tau-Related Faster Clinical Progression. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Koch, G, Di Lorenzo, F, Del Olmo, MFernandez, Bonní, S, Ponzo, V, Caltagirone, C, Bozzali, M, Martorana, A |
Journal | J Alzheimers Dis |
Volume | 50 |
Issue | 2 |
Pagination | 605-16 |
Date Published | 2016 |
ISSN | 1875-8908 |
Keywords | Aged, Alzheimer Disease, Amyloid beta-Peptides, Cognition, Disease Progression, Evoked Potentials, Motor, Female, Humans, Male, Motor Cortex, Neuronal Plasticity, Neuropsychological Tests, Phosphorylation, tau Proteins, Transcranial Magnetic Stimulation |
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. |
DOI | 10.3233/JAD-150813 |
Alternate Journal | J. Alzheimers Dis. |
PubMed ID | 26757193 |