🧫
KEEPS Continuation: Long-term effects of menopausal hormone therapy on AD biomarkers
active
experiment
Created: 2026-04-11T00:48:06
By: etl-v1-backfill
Quality:
50%
✓ SciDEX
ID: exp-d003e659-7083-433b-b1e8-b68107d462b1
🧫 Experiment Protocol
ClinicalAlzheimer's diseaseAPOErecently menopausal women with good cardiovascular healthproposed
This is a follow-up study to the Kronos Early Estrogen Prevention Study (KEEPS) that investigated the long-term effects of short-term menopausal hormone therapy on Alzheimer's disease biomarkers. The original KEEPS trial randomized recently menopausal women with good cardiovascular health to receive either oral conjugated equine estrogens (oCEE), transdermal 17β-estradiol (tE2) with micronized progesterone, or placebo for 4 years. Ten years after completion of the original trial, participants were reassessed using amyloid beta PET imaging, structural MRI to measure hippocampal atrophy and dorsolateral prefrontal cortex thickness. The study aimed to determine whether previous exposure to hormone therapy had any lasting effects on brain health and AD pathophysiology. The researchers also examined whether apolipoprotein E ε4 carrier status modified any observed effects. This represents one of the first long-term follow-up studies of a hormone therapy clinical trial using advanced neuroimaging biomarkers for Alzheimer's disease.
PRIMARY OUTCOME
Amyloid beta burden on PET, hippocampal atrophy, and dorsolateral prefrontal cortex thickness on MRI
EXPECTED OUTCOMES
The study hypothesized that imaging biomarkers would reveal early detection of evolving brain pathology if hormone therapy had long-term effects on AD risk
SUCCESS CRITERIA
- Prespecified primary endpoint (Amyloid beta burden on PET, hippocampal atrophy, and dorsolateral prefrontal cortex thickness on MRI) improves versus control with p < 0.05 or an equivalent corrected threshold used by the study.
- The effect size is biologically meaningful and reproduced across technical/biological replicates or the validation subset.
- Safety, data quality, and missingness remain within protocol-defined bounds so the result is interpretable rather than driven by attrition or assay failure.
PROTOCOL
Participants from the original KEEPS trial were recontacted 10 years after completion. Amyloid beta burden was assessed using positron emission tomography. Structural MRI was performed to measure hippocampal atrophy and dorsolateral prefrontal cortex thickness. APOE ε4 genotyping was performed to assess genetic modifying effects.
LINKED HYPOTHESES
h-seaad-fa5ea82d· APOE Isoform Expression Across Glial Subtypesh-var-600b3e39aa· APOE4-Specific Proteolytic Fragment Inhibition Therapyh-44195347· APOE4 Allosteric Rescue via Small Molecule Chaperonesh-d0a564e8· Competitive APOE4 Domain Stabilization Peptidesh-11795af0· Selective APOE4 Degradation via Proteolysis Targeting Chimeras (PROTACs)
Source: PMID 41618732 ↗
🧫 Experiment Extras
PATHWAY
amyloid beta metabolism, neurodegeneration
MARKET PRICE
$0.50
STATUS
proposed
▸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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