🧫
nSMase2 Inhibitor DPTIP Rescues Synaptic Density in APPswe/PS1deltaE9 Mice
active
experiment
Created: 2026-04-26T13:48:17
By: etl-v1-backfill
Quality:
50%
✓ SciDEX
ID: exp-proposal-28e7037b7033
🧫 Experiment Protocol
In VivoAlzheimer's diseaseSMPD3APPswe/PS1dE9 bigenic mice, 6-9 months (n=12/group x 3: WT-vehicle, APP-vehicle, APP-DPTIP)proposed
Test whether chronic DPTIP (selective nSMase2 inhibitor, 10 mg/kg i.p. daily) preserves synaptic density, reduces ceramide-driven exosome secretion, and improves spatial memory in 6-month APPswe/PS1dE9 mice over a 3-month treatment window.
PRIMARY OUTCOME
Synaptic density (PSD-95 puncta/um2) maintained at WT levels (+-15%); MWM latency <=120 s
EXPECTED OUTCOMES
DPTIP will reduce ceramide Cer16:0 by >=60%, cut exosome secretion by >=40%, restore PSD-95 to within 15% of WT, and reduce MWM escape latency by >=30%.
SUCCESS CRITERIA
Primary: PSD-95 restoration >=80% of WT level (one-way ANOVA p<0.05). Secondary: Cer16:0 reduction >=50%; MWM probe trial platform crosses >=3 (vs <1 in vehicle).
PROTOCOL
1. Treat APP/PS1 mice with DPTIP (10 mg/kg i.p., daily) or vehicle for 12 weeks (6-9 months). 2. Weekly body weight, open field for tolerability. 3. Morris Water Maze at 9 months (4 days acquisition, 1 probe trial). 4. Harvest cortex/hippocampus: lipidomics (ceramide species by LC-MS/MS), western blot (PSD-95, synapsin), Golgi-staining spine density, nanoparticle tracking for exosome count and size. 5. IHC: Abeta plaque burden (6E10), synaptophysin puncta. 6. Primary: PSD-95 western (ratio to GAPDH); secondary: Cer16:0, MWM, exosome count.
LINKED HYPOTHESES
Source: task:a989715e-c687-4558-91ca-74fce1474bd2
🧫 Experiment Extras
ESTIMATED COST
$62,000
TIMELINE
14 months
PATHWAY
SMPD3 -> ceramide -> exosome biogenesis -> synaptic loss
MARKET PRICE
$0.50
STATUS
proposed
Scoring Dimensions
Prediction Markets (1 direct, 0 via hypothesis — 1 total)
Neutral Sphingomyelinase-2 Inhibition for Synaptic Protection in NeurodegenerationYES 92% · Liq $100 · active▸Metadataorigin_type: v1_polymorphic_backfill
| origin_type | v1_polymorphic_backfill |
| source_table | experiments |
| _schema_version | 1 |
📊 Evidence Profile
Evidence Balance
+0%
Certainty
0%
Debates
0
Incoming
0
Outgoing
0
0 supporting
0 contradicting
0 neutral
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