Inflammation in the Parkinson's nigra

The research record

This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".

Who

P. L. McGeer, S. Itagaki, B. E. Boyes and E. G. McGeer, Department of Psychiatry, University of British Columbia, Vancouver (affiliation per PubMed).

What happened

The team stained brain tissue for HLA-DR, a surface molecule that immune cells display when they are "on alert." They found large numbers of HLA-DR-positive reactive microglia, together with Lewy bodies and free melanin, in the substantia nigra of all 5 Parkinson's cases and all 5 cases of parkinsonism with dementia. Similar but less extensive changes appeared in 6 of 9 Alzheimer-type dementia brains and only 1 of 11 age-matched non-neurological controls. They concluded that these microglia are a sensitive index of neuropathological activity. The paper is Neurology 1988;38(8):1285-1291.

Why it moved us toward a cure

It put the immune system on the map of Parkinson's, years before synuclein was known to be in Lewy bodies (landmark 5). Later work reinforced it: a Japanese group found more of these cells as nigral degeneration progressed, with most activated microglia persisting whether or not Lewy bodies were present (Imamura et al. 2003), and brain-imaging (PET) studies reported microglial activation in people with Parkinson's, including early in the disease (cited in a 2019 review). This opened the questions pursued in landmark 38, 53 and 55: do immune cells start the damage, speed it up, or merely clear dead neurons?

Outcome

Open. That inflammation is present is well accepted. Whether it causes neuron loss, and so whether anti-inflammatory treatment can slow the disease, is unproven. Epidemiological studies of anti-inflammatory painkillers (NSAIDs) and Parkinson's risk are mixed, according to the 2019 review; the only specific signals were in subgroups.

Sources

• McGeer PL, Itagaki S, Boyes BE, McGeer EG. "Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson's and Alzheimer's disease brains." Neurology 1988;38(8):1285-1291, DOI 10.1212/wnl.38.8.1285, PMID 3399080 (abstract read; also Alzforum citation page)
• Liu C-Y, Wang X, Liu C, Zhang H-L, "Pharmacological Targeting of Microglial Activation: New Therapeutic Approach", Front Cell Neurosci 2019;13:514, DOI 10.3389/fncel.2019.00514 (summary of the McGeer finding, PET studies and NSAID data)
• Imamura K et al., Acta Neuropathol 2003;106:518-526, DOI 10.1007/s00401-003-0766-2, PMID 14513261 (abstract)
• Not yet verified: the full text of the 1988 paper (abstract only); the PET studies and NSAID meta-analyses (read only as summarised in the 2019 review).