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November 12, 2025Journal of Neuroscience

APOE-Targeted Therapeutics for Alzheimer's Disease

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Authors

HYHussein N YassineCHCristelle HugoBOBernadette O'Donovan

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Overview

Review outlines therapeutic strategies targeting APOE4 mechanisms to mitigate Alzheimer's disease risk and enhance treatment efficacy.

Key Points

  • This review focuses on how APOE4 influences Alzheimer's disease progression and the therapeutic strategies to counteract its effects.
  • Organized effects of APOE4 into three interconnected 'hits' affecting disease progression.
  • Reviewed emerging APOE-related therapeutic approaches targeting lipid handling and inflammation.
  • Explored gene therapies for APOE4 isoform switching and allele silencing.
  • Identified disrupted lipid transport and neuroinflammation as key factors in Alzheimer's risk.
  • Emphasized the need for therapies that go beyond amyloid- and tau-targeting to improve outcomes.
  • Proposed strategies that align with specific APOE4 biology for broader treatment benefits.

Cite This Study

Yassine et al. (2025) studied this question.

synapsesocial.com/papers/69252e83c0ce034ddc355a4fhttps://doi.org/10.1523/jneurosci.1388-25.2025
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1APOE and Alzheimer’s Disease: From Lipid Transport to Physiopathology and Therapeutics2021 · 356 citations
  2. 2ApoE4: an emerging therapeutic target for Alzheimer’s disease2019 · 466 citations
  3. 3Apolipoprotein E4 in Alzheimer’s Disease: Role in Pathology, Lipid Metabolism, and Drug Treatment2026 · 5 citations
  4. 4Apolipoprotein E (APOE) in Alzheimer’s Disease: Mechanisms, Modifiers, and Therapeutic Implications2026
  5. 5APOE4 reprograms microglial lipid metabolism in Alzheimer's disease: Mechanisms and therapeutic implications2025 · 20 citations