4.6 Article

Age at Disease Onset Associates With Oxidative Stress, Neuroinflammation, and Impaired Synaptic Plasticity in Relapsing-Remitting Multiple Sclerosis

Journal

FRONTIERS IN AGING NEUROSCIENCE
Volume 13, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fnagi.2021.694651

Keywords

aging; relapsing remitting multiple sclerosis; progression of disability independent of disease activity; synaptic plasticity; neuroinflammation; oxidative stress

Funding

  1. FISM Grants (Fondazione Italiana Sclerosi Multipla) [2019/S/1]
  2. National Funding of the Italian Ministry of Universities and Research (MIUR-PRIN 2017) [2017K55HLC]
  3. Italian Ministry of Health [RF-2018-12366144]

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In patients with RR-MS, older age at onset is associated with reduced disease activity, increased oxidative stress, enhanced central inflammation, and altered synaptic plasticity. Older patients show less clinical and radiological focal inflammatory disease activity, but have higher levels of lactate and pro-inflammatory molecules in their cerebrospinal fluid, with a negative correlation between age and synaptic plasticity evidenced by TMS.
Age at onset is the main risk factor for disease progression in patients with relapsing-remitting multiple sclerosis (RR-MS). In this cross-sectional study, we explored whether older age is associated with specific disease features involved in the progression independent of relapse activity (PIRA). In 266 patients with RR-MS, the associations between age at onset, clinical characteristics, cerebrospinal fluid (CSF) levels of lactate, and that of several inflammatory molecules were analyzed. The long-term potentiation (LTP)-like plasticity was studied using transcranial magnetic stimulation (TMS). Older age was associated with a reduced prevalence of both clinical and radiological focal inflammatory disease activity. Older patients showed also increased CSF levels of lactate and that of the pro-inflammatory molecules monocyte chemoattractant protein 1 (MCP1)/CCL2, macrophage inflammatory protein 1-alpha (MIP-1 alpha)/CCL3, and interleukin (IL)8. Finally, TMS evidenced a negative correlation between age and LTP-like plasticity. In newly diagnosed RR-MS, older age at onset is associated with reduced acute disease activity, increased oxidative stress, enhanced central inflammation, and altered synaptic plasticity. Independently of their age, patients with multiple sclerosis (MS) showing similar clinical, immunological, and neurophysiological characteristicsmay represent ideal candidates for early treatments effective against PIRA.

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