Clinical PD symptoms include dopa-responsive motor symptoms and dopa-resistant non motor symptoms. Some of the non motor symptoms begin during the premotor stage, like constipation, hyposmia or REM-sleep disorders. Dementia, gait disorders and dysarthria occur in later stages of the disease.
PD pathology extends well beyond the substantia nigra. It affects autonomic and non autonomic nuclei in the brainstem and in the medulla, the olfactory bulb and the peripheral autonomic nervous system. Alpha-synuclein aggregates, called Lewy bodies and Lewy neurites, are detectable in these structures at early stages.
The study of the enteric nervous system (ENS) displays the Lewy pathology in living patients through the digestive biopsies. Minor salivary glands analysis could be a good marker as well, but this needs confirmation.
An anatomopathologic PD biomarker would be interesting at different stages of PD: for the positive diagnosis, to follow the progression and to develop neuroprotective treatments.