Cognitive and cortical plasticity deficits correlate with altered amyloid-β CSF levels in Multiple Sclerosis

Francesco Mori (1) , Silvia Rossi (1) , Giulia Sancesario (1) , Claudia Codecà (1) , Giorgia Mataluni (1) , Fabrizia Monteleone (1) , Fabio Buttari (1) , Hajime Kusayanagi (1) , Maura Castelli (1) , Caterina Motta (1) , Valeria Studer (1) , Giorgio Bernardi (1) , Giacomo Koch (1) , Sergio Bernardini (1) , Diego Centonze (1)

1 Neuroscience

Cognitive dysfunction is of frequent observation in Multiple Sclerosis (MS). It is associated with grey matter pathology, brain atrophy and altered connectivity, and recent evidence showed that acute inflammation can exacerbate mental deficits independently of the primary functional system involved. In the present study, we measured cerebrospinal fluid (CSF) levels of amyloid-β1-42 and tau protein in MS and in Clinical Isolated Syndrome (CIS) patients, since both proteins have been associated with cognitive decline in Alzheimer's disease (AD). In AD, amyloid-β1-42 accumulates in the brain as insoluble extracellular plaques, possible explaining why soluble amyloid-ß1-42 is reduced in the CSF of these patients. In our sample of MS patients, amyloid-β1-42 levels were significantly lower in patients cognitively impaired and were inversely correlated with the number of Gadolinium-enhancing (Gd+) lesions at the magnetic resonance imaging (MRI). Positive correlations between amyloid-β1-42 levels and measures of attention and concentration were also found. Furthermore, abnormal neuroplasticity of the cerebral cortex, explored with theta burst magnetic stimulation (TBS), was observed in cognitively impaired patients, and a positive correlation was found between amyloid-β1-42 CSF contents and the magnitude of long-term potentiation (LTP)-like effects induced by TBS. No correlation was conversely found between tau protein concentrations and MRI findings, cognitive parameters, and TBS effects in these patients. Together, our results indicate that in MS central inflammation is able to alter amyloid-β metabolism, by reducing its concentration in the CSF, and leading to impairment of synaptic plasticity and cognitive function.

Mots clés: Neurodegeneration; Neuroprotection; Alzheimer's Disease; Cognition; Plasticity; inflammation; LTP; tau protein; transcranial magnetic stimulation

Francesco Mori, Silvia Rossi, Giulia Sancesario, Claudia Codecà, Giorgia Mataluni, et al.. Cognitive and cortical plasticity deficits correlate with altered amyloid-β CSF levels in Multiple Sclerosis. Neuropsychopharmacology, 2010, ⟨10.1038/npp.2010.187⟩. ⟨hal-00585468⟩