This Is MS Multiple Sclerosis Community: Knowledge & Support

Because diseases such as Alzheimer’s and Parkinson’s have a much more prominent
degenerative rather than inflammatory phenotype, the initial assumption was that a degenerative
mechanism (or mechanisms) was primarily responsible, with inflammation perhaps a secondary,
but possibly important, consequence of the degeneration. In MS, the situation is reversed:
inflammation occurs early and is very prominent in many patients, so it was naturally assumed that
autoimmunity might be causal; but, as we argue throughout this Perspective, such an assumption
may be incorrect. If MS is primarily a degenerative disorder in line with an inside-out mechanism,
why would this disease be unique in engendering such prominent and cyclic inflammation?

The differences may be related to age: Alzheimer’s disease and Parkinson’s disease present decades
later than MS, and immune responsiveness wanes with age through a process of ‘immune
senescence’ (REFS 21,87). Indeed, the responsiveness of T cells, which are known to be centrally
involved in the immunopathogenesis of MS88, appears to be particularly altered with age87.
Moreover, it is conceivable that the putative cytodegeneration involving the myelinating unit
(oligodendroglia, their processes and myelin) in MS releases debris that is more antigenic35,36,66 than
the debris that is shed from the mainly synaptic and neuronal degeneration in Alzheimer’s disease.