Cognitive and cortical plasticity deficits correlate with altered amyloid-Β CSF levels in multiple sclerosis

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

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Cognitive dysfunction is of frequent observation in multiple sclerosis (MS). It is associated with gray 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 this study, we measured cerebrospinal fluid (CSF) levels of amyloid-Β 142 and protein in MS and in clinically isolated syndrome patients, as both proteins have been associated with cognitive decline in Alzheimer's disease (AD). In AD, amyloid-Β 1-42 accumulates in the brain as insoluble extracellular plaques, possibly explaining why soluble amyloid-Β 1-42 is reduced in the CSF of these patients. In our sample of MS patients, amyloid-Β 1-42 levels were significantly lower in patients cognitively impaired (CI) and were inversely correlated with the number of Gadolinium-enhancing (Gd) lesions at the magnetic resonance imaging (MRI). Positive correlations between amyloid-Β 1-42 levels and measures of attention and concentration were also found. Furthermore, abnormal neuroplasticity of the cerebral cortex, explored with burst stimulation (TBS), was observed in CI patients, and a positive correlation was found between amyloid-Β 1-42 CSF contents and the magnitude of long-term potentiation-like effects induced by TBS. No correlation was conversely found between 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.

Original languageEnglish
Pages (from-to)559-568
Number of pages10
JournalNeuropsychopharmacology
Volume36
Issue number3
DOIs
Publication statusPublished - Feb 2011

Fingerprint

Amyloid
Multiple Sclerosis
Cerebrospinal Fluid
Neuronal Plasticity
Alzheimer Disease
Magnetic Resonance Imaging
Inflammation
Amyloidogenic Proteins
Long-Term Potentiation
Gadolinium
Brain
Cerebral Cortex
Cognition
Atrophy
Proteins
Observation
Pathology

Keywords

  • cognition
  • inflammation
  • LTP
  • t protein
  • transcranial magnetic stimulation

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

Cite this

Cognitive and cortical plasticity deficits correlate with altered amyloid-Β CSF levels in multiple sclerosis. / Mori, Francesco; Rossi, Silvia; Sancesario, Giulia; Codecá, Claudia; Mataluni, Giorgia; Monteleone, Fabrizia; Buttari, Fabio; Kusayanagi, Hajime; Castelli, Maura; Motta, Caterina; Studer, Valeria; Bernardi, Giorgio; Koch, Giacomo; Bernardini, Sergio; Centonze, Diego.

In: Neuropsychopharmacology, Vol. 36, No. 3, 02.2011, p. 559-568.

Research output: Contribution to journalArticle

Mori, F, Rossi, S, Sancesario, G, Codecá, C, Mataluni, G, Monteleone, F, Buttari, F, Kusayanagi, H, Castelli, M, Motta, C, Studer, V, Bernardi, G, Koch, G, Bernardini, S & Centonze, D 2011, 'Cognitive and cortical plasticity deficits correlate with altered amyloid-Β CSF levels in multiple sclerosis', Neuropsychopharmacology, vol. 36, no. 3, pp. 559-568. https://doi.org/10.1038/npp.2010.187
Mori, Francesco ; Rossi, Silvia ; Sancesario, Giulia ; Codecá, Claudia ; Mataluni, Giorgia ; Monteleone, Fabrizia ; Buttari, Fabio ; Kusayanagi, Hajime ; Castelli, Maura ; Motta, Caterina ; Studer, Valeria ; Bernardi, Giorgio ; Koch, Giacomo ; Bernardini, Sergio ; Centonze, Diego. / Cognitive and cortical plasticity deficits correlate with altered amyloid-Β CSF levels in multiple sclerosis. In: Neuropsychopharmacology. 2011 ; Vol. 36, No. 3. pp. 559-568.
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