Friday, 20 June 2014

Is inflammation in the MS the same as in other neurodegenerative diseases

Filiou MD, Arefin AS, Moscato P, Graeber MB. 'Neuroinflammation' differs categorically from inflammation: transcriptomes of Alzheimer's disease, Parkinson's disease, schizophrenia and inflammatory diseases compared. Neurogenetics. 2014 Jun 15. [Epub ahead of print]

Neuroinflammation' has become a widely applied term in the basic and clinical neurosciences but there is no generally accepted neuropathological tissue correlate. Inflammation, which is characterized by the presence of perivascular infiltrates of cells of the adaptive immune system, is indeed seen in the central nervous system (CNS) under certain conditions. Authors who refer to microglial activation as neuroinflammation confuse this issue because autoimmune neuroinflammation serves as a synonym for multiple sclerosis, the prototypical inflammatory disease of the CNS. We have asked the question whether a data-driven, unbiased in silico approach may help to clarify the nomenclatorial confusion. 
Specifically, we have examined whether analysis of microarray data obtained from human cerebral cortex of Alzheimer's, Parkinson's and schizophrenia patients would reveal a degree of relatedness between these diseases and recognized inflammatory conditions including multiple sclerosis. Our results using two different data analysis methods provide strong evidence against this hypothesis demonstrating that very different sets of genes are involved. Consequently, the designations inflammation and neuroinflammation are not interchangeable. They represent different categories not only at the histophenotypic but also at the transcriptomic level. Therefore, non-autoimmune neuroinflammation remains a term in need of definition.

There are immune cells activated in multiple sclerosis and to a lesser extent in other neurodegenerative diseases, This study asks are they all the same. This study looked at protein production messages (microarray)  of a number of neurodegenerative conditions and found that active MS was more like active autoimmune diseases like bowel disease, rather than classical neurodegenerative diseases such as Altzheimers disease and Parkinsons Disease. The adaptive (lymphocyte) containing lesions are different from the microglial inflammation in the other autoimmune diseases and less like inflammatory disease and perhaps if a hot glial inflammation was compared to the neurodegenerative lesions then there may have been more similarities, but they were compared to active MS lesion and if you compare orange with lemons you may expect changes 


  1. MD,

    My thinking has been that in MS inflammation begets neurodegeneration, just as in rheumatoid arthritis the inflammation later causes osteoarthritis of the already damaged joints. I know from reading your blog that others think that the two processes are somehow separate and others suggest that neurodegeneration causes inflammation in MS. In the latter case, I can't think of another condition in the body where a degenerative process causes inflammation (but correct me if I'm wrong).

    Do you think the chicken and egg problem with MS is sufficiently sorted, or are more studies like this one required?

    Thanks as always

  2. I'd prefer the inflammation in MS to be more like autoimmune diseases not neurodegenerative diseases. MS does appear to have similarities with autoimmune disease e.g. gender difference (more women than men), other autoimmune diseases run in families where there are MSers etc.

    My question - when are we likely to be able to set out what happens in MS i.e. what is the order of events leading to end organ damage. Surely this is the most important question to answer, but research over the last 50 years (despite huge advances in technology) doesn't seem to make any headway.

    1. The answer has already been given almost thirty years ago. It is still waiting for medical science to mature. This can be extremely hard at times. Scientific revolution comes when obsolete ideas die with their bearers. Unfortunately, obsolescence in MS research is routinely disguised as progress.

  3. Mouse Dr,

    Is there any evidence that the 'neurodegeneration' of MS is all a consequence of multiple inflammatory lesions over time and that these lesions are only sometimes large enough to appear as a full blown relapse or as an overt abnormality on MR. The rest of the time they are beyond clinical and imaging detection. In other words it is all the same pathological process but to a different scale? As with many autoimmune diseases this inflammatory portion eventually burns out leaving the degeneration which will have become clinically evident either before or after this happens.

    Thanks for all your hard work

    1. Could be..if you look at the pathology the lesions are often similar. In the animals the lesion associated with the attack is a bit different from what we see in relapse,

  4. "......perhaps if a hot glial inflammation was compared to the neurodegenerative lesions......"

    Are you implying that they did not compare activated microglia in the different diseases? I think this is the whole point of the paper:

    "Authors who refer to microglial activation as neuroinflammation confuse this issue......"

    So I guess you must have a distinction between activated microglia and "hot" microglia.

    1. I think you are right in this was the idea, but I am not sure they are comparing microglia they are comparing lesions.So in the MS case it was described as an active lesion so it could be T and B cells and macrophages in addition to microglia..I wonder if white matter would have been a better comparison to the other brain lesion. Maybe I need to read again


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