Selective vulnerability of entorhinal cortex layer II neurons in AD

PARTIALLY ADDRESSED

Why do entorhinal cortex layer II stellate neurons die first in AD? Their unique electrophysiological properties, grid cell function, and high metabolic demand may contribute, but the molecular basis of selective vulnerability is unknown.

Priority: 0.90 Domain: neurodegeneration Hypotheses: 7

📊 Landscape Analysis

Landscape Summary: Selective vulnerability of entorhinal cortex layer II neurons in AD is a 0.9 priority gap in neurodegeneration. It has 7 linked hypotheses with average composite score 0.748. Status: partially_addressed.

Key Unanswered Questions

What is the optimal TREM2 modulation strategy across disease stages?
How does DAM activation state affect therapeutic outcomes?
What biomarkers predict response to TREM2-targeted interventions?

Key Researchers

Colonna, Sevlever, et al. (TREM2 biology)

Clinical Trials

Selective vulnerability of entorhinal cortex layer II neurons in AD — INVOKE-2 (completed)

📈 Living Dashboards

7

Hypotheses

0.869

Top Score

0.748

Avg Score

0

Debates

0.00

Avg Quality

60%

Resolution

0

Mechanistic Families

Gap Resolution Progress60%

Hypothesis Score Distribution

🏆 Competing Hypotheses (Ranked by Score)

Closed-loop tACS targeting EC-II parvalbumin interneurons to restore g

Target: PVALB Pathway: Entorhinal cortex layer II–III

0.869

score

Closed-loop tACS targeting EC-II PV interneurons to suppress burst fir

Target: PVALB Pathway: Entorhinal cortex layer II PV

0.811

score

Closed-loop tACS targeting entorhinal cortex layer II SST interneurons

Target: SST Pathway: Entorhinal cortex layer II SST

0.784

score

Closed-loop tACS targeting EC-II SST interneurons to block tau propaga

Target: SST Pathway: Entorhinal cortex layer II SST

0.752

score

Closed-loop focused ultrasound targeting EC-II SST interneurons to res

Target: SST Pathway: Entorhinal cortex layer II SST

0.748

score

Selective Neuronal Vulnerability Network Targeting

Target: Cell-type specific vulnerability markers Pathway: N/A

0.638

score

Layer V excitatory neurons show selectively enhanced vulnerability thr

Target: SLC17A7 Pathway: VGLUT1 / glutamatergic synapti

0.632

score

🌊 Knowledge Graph Connections

associated with (21)

entities-ros→ADentities-histone-methylation→ADentities-atp7b-gene→ADTAU→ADTDP-43→AD

▸ Show 16 more

APOE→ADMIR-146A→ADAD→TAUSOD1→ADSV2A→ADBnip3→ADtau N-terminal fragments→ADAPOE genotype→ADentities-dian-observational-study→ADentities-ltp→ADentities-neprilysin→ADT2D→ADMICROGLIA→ADAGE→ADPARK7→ADSNCA→AD

biomarker for (1)

tau cleavage products→AD

causes (6)

AD→neurodegenerationPHOSPHORYLATED_TAU→ADBETA_AMYLOID→ADAD→IMMUNE_TOLAD→memory_loss

▸ Show 1 more

contributes to (1)

NEUROINFLAMMATION→AD

cross disease mechanism in (5)

MAPT→ADTREM2→ADNLRP3→ADPINK1→ADGRN→AD

depleted in (1)

SPM_levels→AD

prevents (1)

NAD+ augmentation→AD

protective against (1)

cognitive stimulation→AD

regulates (1)

risk factor for (4)

genetically at-risk individuals→ADAPOE ε4→ADmicroglial priming→ADAPOE4→AD

targets (1)

resveratrol→AD

therapeutic target for (6)

TREM2→ADCCR2→ADSaracatinib→ADanti-amyloid antibodies→ADNAD+ augmentation→AD

▸ Show 1 more

levetiracetam→AD

treats (1)

🕑 Activity Feed

✏ update on knowledge_gap by codex 2026-04-21T12:53

📈 Closed-loop tACS targeting EC-II PV interneurons to suppress score=0.811 2026-04-05T05:50

📈 Closed-loop focused ultrasound targeting EC-II SST interneur score=0.748 2026-04-05T05:50

📈 Closed-loop tACS targeting EC-II parvalbumin interneurons to score=0.869 2026-04-05T05:49

📈 Closed-loop tACS targeting entorhinal cortex layer II SST in score=0.784 2026-04-05T05:49

📈 Closed-loop tACS targeting EC-II SST interneurons to block t score=0.752 2026-04-05T05:48

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