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

Mario Stampanoni Bassi, Luana Gilio, Ennio Iezzi, Alessandro Moscatelli, Tatjana Pekmezovic, Jelena Drulovic, Roberto Furlan, Annamaria Finardi, Georgia Mandolesi, Alessandra Musella, Giovanni Galifi, Roberta Fantozzi, Paolo Bellantonio, Marianna Storto, Diego Centonze, Fabio Buttari

Research output: Contribution to journalArticlepeer-review

Abstract

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 (MCP-1)/CCL2, macrophage inflammatory protein 1-alpha (MIP-1α)/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 characteristics may represent ideal candidates for early treatments effective against PIRA.

Original languageEnglish
Pages (from-to)694651
JournalFrontiers in Aging Neuroscience
Volume13
DOIs
Publication statusPublished - 2021

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