(continuation of cohort columns from 20240722_183358) | (Huh, 2020 #1105) | (Stoker, 2020 #1146) #250 | (Minett, 2018 #1234) | (Crilia, 2016 #163) | (Malek, 2018 #549) | (Davis, 2016 #192) | 2023 Ppmi annual investigator meeting (May 4) | 2023 Ppmi investigator meeting (May 3 & 4) | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| DATScan | The program will run over the next 2.5-3 years using NovaSeq X Plus, Illumina's most powerful high-throughput sequencer, with its 25B flow cell, library preparation kits and analysis software to generate the whole-genome sequencing data. | |||||||||||
| Motor tracking | O | MDS-UPDRS on the first 3000. For the next 12,000 for financial reasons, we removed | ||||||||||
| Cognition | O | o | O | Comprehensive cog battery | ||||||||
| sMRI | X | O | ||||||||||
| Effect size | O | |||||||||||
| CSF | X | O | ||||||||||
| Blood | O | O | O | O | ||||||||
| Publication/Resource | (Huh, 2020 #1105) | (Stoker, 2020 #1146) #250, Pathogenic variants & non-pathogenic variants 보누 나음에서 (비슷안 성노도) rapid progression 보님 : time to HY3, Postural instability, time to dementia (54% had dementia at 10 year follow-up vs 32% in non-carriers), MRI 없음. | (Minett, 2018 #1234) DTI-focused. 27 PD-MCI vs 93 PD-normal cognition, 18m F/U, No genotype | (Crilia, 2016 #163) | (Malek, 2018 #549) | (Davis, 2016 #192) Mean (SD) Annual change of MDS-UPDRS-III 3.4 (7.7) 2.0 (6.6) | ||||||
| AMP-PD = PPMI + PDBP | variants 보누 나음에서 (비슷안 progression 보님 : time to HY3, Postural instability, time to dementia (54% had dementia at 10 year follow-up vs 32% in non-carriers), MRI 93 PD-normal cognition, 18m F/U, No genotype | |||||||||||
| (Firbank, 2017 #1235) FDG-PET, No genotype | ||||||||||||
| (Nombela, 2014 #1236) genotype o (but no GBA). | ||||||||||||
4 LRRK2
Animal models of LRRK2
a. although they show α-syn or ubiquitin accumulation, progressive motor impairments, and slight reduction of striatal DA, they do not display functional disruption of the nigrostriatal dopaminergic neurons [82, 124–128]. b. overexpression of G2019S or R1441C LRRK2 ii. leads to none or slight loss of dopaminergic neurons in the SNpc and no alteration in striatal DA levels or locomotor activity in both mice and rats c. BAC transgenic mice with mutated LRRK2 iii. No nigrostriatal degeneration d. rat LRRK2 model with neuron-specific, adenoviral mediated expression of LRRK2 G2019S in the nigrostriatal system iv. → a progressive degeneration of nigral dopaminergic neurons [135 e. expression of G2019S LRRK2 v. 50% neuronal loss in the ipsilateral SNc associated with reduced striatal dopaminergic fibers [136]. f. codes for LRRK2 g. LRRK2 is a large gene with 51 exons, spanning a genomic region of 144 kb. It contains five functional domains including a leucine rich repeat domain.
Figure 1. Schematic representation of the 144-kb LRRK2 loci on chromosome 12q12. The estimated start of the Lrrk2 domain structure is indicated by the residue number (690) below the exonic-intronic (Ex1-Ex51) and domain scheme. Domains:
- ANK = ankyrin repeat region
- LRR = leucine-rich repeat
- Roc = Ras of complex; GTPase
- COR = C terminal of Ras
- MAPKKK = MAPK kinase kinase
- WD40
Inflammation and LRRK2
(Section heading visible on the page; body content begins on the following page 20240722_183404.)
Uncertain Spans
| location | transcription | uncertainty |
|---|---|---|
Longitudinal table / DATScan-row long descriptor cell | ”The program will run over the next 2.5-3 years using NovaSeq X Plus, Illumina’s most powerful high-throughput sequencer, with its 25B flow cell, library preparation kits and analysis software to generate the whole-genome sequencing data.” | This long descriptor cell spans many narrow columns of the wide table; column placement collapsed in the HTML rendering, but the original text is preserved verbatim. |
Longitudinal table / Davis 2016 #192 cell | reads Mean (SD) Annual change of MDS-UPDRS-III / 3.4 (7.7) / 2.0 (6.6) with yellow background highlight on the header phrase. | low confidence on whether 3.4 (7.7) and 2.0 (6.6) are paired with two different sub-columns or both belong to a single Mean (SD) column. |
Inflammation and LRRK2 | section heading visible at the bottom edge of the photo; body bullets are not visible in this slice and continue on 20240722_183404. | section break across photos; not a value uncertainty. |