We all have advanced PD? Can't remember where I heard that but it left an impression. Sadly, it is true. Scientists at UC San Fran are finding that dopamine alteration takes place years before motor symptoms appear. They suggest that earliest signs could be constipation or REM Sleep Disorder long before a tremor or a mysteriously cramping foot.

For some reason as Alpha-Synuclein begins to aggregate it inhibits Dopamine release in our synapses causing a major communication breakdown between neurotransmitters. This results in misfired synapses and missed signals between the brain and body and our motor symptoms. The researchers have grown neurons in the lab and are still observing how it all happens. They think one of the first stages of the disease is synaptic damage. Well, this highlights how important biomarkers are. Article

Note what the lead researcher has to say about this finding:


The loss of function in Parkinson’s disease that is attributed to loss of neurons in the brain may in part be due to impaired signaling.

“Even people with advanced Parkinson’s still have a substantial number of dopamine-producing neurons that remain. Our prediction is that even the neurons that survive don’t work very well, due to functional impairment at synapses.”

This finding shifts the focus in Parkinson’s from cell loss to the much earlier phenomenon of synaptic dysfunction -- something that will be much more amenable to treatment,” Edwards says.

This may explain some of the PD negative DATscans. Just how much our disease is dopamine cell loss vs. Alpha syn. interference at the synaptic vessel? This opens up some new avenues for therapy and a cure (or cures?) :P

Also may explain widely varying levels of patient response to levodopa?

It raises many questions....