Data from: Loss of primary cilia and dopaminergic neuroprotection in pathogenic LRRK2driven and idiopathic Parkinson’s disease

Activating LRRK2 mutations cause Parkinson’s disease. Previously, we
showed that cholinergic interneurons and astrocytes but not medium spiny
neurons of the dorsal striatum lose primary cilia in LRRK2 mutant mice.
Single nucleus RNA sequencing shows that cilia loss in cholinergic
interneurons correlates with higher LRRK2 expression and decreased glial
derived neurotrophic factor transcription. Nevertheless, much higher LRRK2
expression is seen in medium spiny neurons that have normal cilia in mice
and humans. In parallel with decreased striatal dopaminergic neurite
density, LRRK2 G2019S neurons show increased autism-linked CNTN5 adhesion
protein expression; glial cells show significant loss of ferritin heavy
chain. Human striatal tissue from LRRK2 pathway mutation carriers and
idiopathic Parkinson’s disease show similar cilia loss in cholinergic
interneurons and astrocytes and overall loss of such neurons. These data
strongly suggest that loss of cilia in specific striatal cell types
decreases neuroprotection for dopamine neurons in mice and human
Parkinson’s disease.