Parkinson's disease — LRRK2 (wild-type and G2019S)

Metabolic syndrome components would shape the clinical picture of LRRK2- and GBA-associated Parkinson's disease and the prodromal burden in unaffected carriers.

Across 562 participants (idiopathic, LRRK2 and GBA Parkinson's, non-manifesting carriers and non-carrier controls), the number of metabolic syndrome components did not differ between Parkinson's groups (p = 0.101) or between carrier groups (p = 0.685).

Why it matched: shares LRRK2 · same research area

GSK-3 beta inhibition would reduce tau hyperphosphorylation and slow decline in mild-to-moderate Alzheimer's.

CSF p-tau181 dropped by 28% but ADAS-Cog showed no difference from placebo; the high-dose arm was halted for safety.

Why it matched: shares MAPT/tau · mechanism: Proteostasis

Early clearance of amyloid plaques via monoclonal antibody would slow cognitive decline in prodromal patients.

Plaque burden dropped on PET imaging but ADAS-Cog scores showed no separation from placebo at 18 months.

Why it matched: shares MAPT/tau · mechanism: Proteostasis

Because knocking out Sting prevented neurodegeneration in Pink1/Prkn-deficient mice under mitochondrial stress, removing Sting in Drosophila would likewise rescue Pink1/parkin mutant defects.

Loss of Sting, or of its downstream effector Relish, did not suppress the behavioural deficits or the mitochondrial disruption of Drosophila Pink1 or parkin mutants, nor of an mtDNA mutator model.

Why it matched: same research area · failed the same way: Held in the model species, not beyond it

Long-term voluntary running would reduce insoluble amyloid, neuroinflammation and non-cognitive behavioural problems in the 5xFAD mouse model of Alzheimer's disease.

After 24 weeks of wheel running started before heavy plaque formation (female mice, n = 30), microglia, cytokines and insoluble amyloid-beta were unchanged. Runners actually developed hindlimb clasping earlier (p = 0.009) and showed more anxiety-like and exploratory behaviour.

Why it matched: mechanism: Proteostasis · failed the same way: Held in the model species, not beyond it