PET shows microglial activation in life

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

Alexander Gerhard, N. Pavese, David Brooks, Richard Banati and colleagues, MRC Clinical Sciences Centre, Imperial College London (Medical Research Council funding per PubMed). Neurobiol Dis 21:404–412, 2006.

What happened

Earlier evidence for immune activation (landmark 52) came from autopsy tissue. This study used PET (positron emission tomography, a scan that tracks a radioactive tracer) with [11C](R)-PK11195, which binds to sites that microglia (the brain's immune cells) display when activated.

• 18 people with Parkinson's and 11 healthy controls were scanned. The patients also had a dopamine-terminal PET scan.
• Tracer binding was significantly higher in patients in the pons (part of the brainstem), the basal ganglia, and frontal and temporal cortex.
• Eight patients were rescanned for 2 years; the signal stayed stable.
• Microglial activation did not correlate with clinical severity or with putamen dopamine uptake.

The authors concluded that the absence of change over 2 years suggests microglia are activated early and then stay roughly constant, possibly driving the disease through cytokine release (inflammatory signalling molecules). This is their interpretation.

Why it moved us toward a cure

It showed inflammation can be quantified in living patients, giving a way to test whether an anti-inflammatory drug engages its target. It also hinted that the immune response is early, which is the right time to intervene. It did not show that microglia cause the damage.

Outcome

Open. The study was small (18 patients, 8 rescanned), and the tracer measures activation in general, not whether it helps or harms. The authors did not claim it as a diagnostic.

Sources

• Gerhard et al., Neurobiol Dis 2006;21:404–412, DOI 10.1016/j.nbd.2005.08.002, PMID 16182554 (abstract and affiliations via PubMed)
• Not yet verified: the limits of PK11195 and any newer tracers; later PET studies; whether PET microglia imaging is used only for research (removed from the text as unsourced).