Loss of the lysosomal lipid flippase ATP10B leads to progressive dopaminergic neurodegeneration and parkinsonian motor deficits.

# README

Loss-of-function mutations in the ATP10B gene have been identified in Parkinson’s disease patients, pointing to ATP10B as a candidate genetic risk factor. We induced ATP10B knockdown specifically in substantia nigra pars compacta neurons of rats using viral vector technology. Two different microRNA-based shRNA constructs targeting distinct regions of the ATP10B mRNA were used to cross-validate the findings : miRNA5 and miRNA7, and for controls scrambled miRNA was used. A CT and a PE2I PET scan were acquired at different times after the intervention.
Rats were injected at the age of 11-12 weeks old.

This study consists of 3 cohorts:
- Cohort SCRControl (10 subjects): Scrambled miRNA SCR
- Cohort miR5ATP10BKD (10 subjects): miRNA miR5 against (KD) ATP10B
- Cohort miR7ATP10BKD (5 subjects): miRNA miR7 against (KD) ATP10B

Sessions:
All cohorts consist of 4 session(s):
- Session 01PE2ICT : 2-4 months post intervention, scans = 1 pet, 1 ct, tracer is [18F]PE2I, no blood data
- Session 02PE2ICT : 4-6 months post intervention, scans = 1 pet, 1 ct, tracer is [18F]PE2I, no blood data
- Session 03PE2ICT : 7-9 months post intervention, scans = 1 pet, 1 ct, tracer is [18F]PE2I, no blood data
- Session 04PE2ICT : 12 months post intervention, scans = 1 pet, 1 ct, tracer is [18F]PE2I, no blood data

Missing data:
Some rats died during the study, some others joined the study later than at first session, so most rats were actually not scanned at all 4 sessions.

Sessions undergone by each subject:
- sub-001: 01PE2ICT, 02PE2ICT
- sub-002: 01PE2ICT, 02PE2ICT
- sub-003: 01PE2ICT, 02PE2ICT, 03PE2ICT
- sub-004: 01PE2ICT, 02PE2ICT
- sub-005: 01PE2ICT, 02PE2ICT, 03PE2ICT
- sub-006: 01PE2ICT, 02PE2ICT
- sub-007: 01PE2ICT, 02PE2ICT, 03PE2ICT, 04PE2ICT
- sub-008: 01PE2ICT, 02PE2ICT
- sub-009: 04PE2ICT
- sub-010: 04PE2ICT
- sub-011: 01PE2ICT, 02PE2ICT
- sub-012: 01PE2ICT, 02PE2ICT, 03PE2ICT, 04PE2ICT
- sub-013: 01PE2ICT, 02PE2ICT, 03PE2ICT, 04PE2ICT
- sub-014: 01PE2ICT, 02PE2ICT
- sub-015: 01PE2ICT, 02PE2ICT, 03PE2ICT
- sub-016: 01PE2ICT, 02PE2ICT, 03PE2ICT, 04PE2ICT
- sub-017: 01PE2ICT, 02PE2ICT, 03PE2ICT
- sub-018: 01PE2ICT, 02PE2ICT
- sub-019: 04PE2ICT
- sub-020: 04PE2ICT
- sub-021: 03PE2ICT, 04PE2ICT
- sub-022: 03PE2ICT
- sub-023: 03PE2ICT
- sub-024: 04PE2ICT
- sub-025: 04PE2ICT

Contact person:
Prof. Veerle Baekelandt ([e-mail])

Study year:
2022