Lancet neurology
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Review
Mechanisms of glutamate toxicity in multiple sclerosis: biomarker and therapeutic opportunities.
Research advances support the idea that excessive activation of the glutamatergic pathway plays an important part in the pathophysiology of multiple sclerosis. Beyond the well established direct toxic effects on neurons, additional sites of glutamate-induced cell damage have been described, including effects in oligodendrocytes, astrocytes, endothelial cells, and immune cells. ⋯ Understanding of the mechanisms underlying glutamate toxicity in multiple sclerosis could help in the development of new approaches for diagnosis, treatment, and follow-up in patients with this debilitating disease. While several clinical trials of glutamatergic modulators have had disappointing results, our growing understanding suggests that there is reason to remain optimistic about the therapeutic potential of these drugs.
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Brain amyloid β (Aβ) deposition and neurodegeneration have been documented in about 50-60% of cognitively healthy elderly individuals (aged 60 years or older). The long-term cognitive consequences of the presence of Alzheimer's disease pathology and neurodegeneration, and whether they have an independent or synergistic effect on cognition, are unclear. We aimed to characterise the long-term clinical and cognitive trajectories of healthy elderly individuals using a two-marker (Alzheimer's disease pathology and neurodegeneration) imaging construct. ⋯ CSIRO Flagship Collaboration Fund and the Science and Industry Endowment Fund (SIEF), National Health and Medical Research Council, the Dementia Collaborative Research Centres programme, McCusker Alzheimer's Research Foundation, and Operational Infrastructure Support from the Government of Victoria.