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Neuropsychopharmacology. 2011 Feb;36(3):559-68. doi: 10.1038/npp.2010.187. Epub 2010 Oct 13.

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

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1
Dipartimento di Neuroscienze, Clinica Neurologica, Università Tor Vergata, Rome, Italy.

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(1-42) and τ 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 θ 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 τ 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.

PMID:
20944553
PMCID:
PMC3055691
DOI:
10.1038/npp.2010.187
[Indexed for MEDLINE]
Free PMC Article
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