ArticleAlzheimer's & dementia (New York, N. Y.)
Pharmacodynamic and stage-dependent therapeutic efficacy of SFRP1 neutralization in a mouse model of Alzheimer's disease.
Article in Alzheimer's & dementia (New York, N. Y.). The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Pharmacodynamic and stage-dependent therapeutic efficacy of SFRP1 neutralization in a mouse model of Alzheimer's disease.Alzheimer's & dementia (New York, N. Y.)Article
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6 authors.
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Abstract
introductionAlzheimer's disease (AD) is characterized by early synaptic dysfunction followed by progressive amyloid beta (Aβ) accumulation, neuroinflammation, and cognitive decline. We previously identified secreted frizzled-related protein 1 (SFRP1) as a multifactorial contributor to AD pathogenesis and provided initial evidence that its neutralization ameliorates pathological AD-like traits in mice. Here we evaluate the pharmacodynamics, biodistribution, and therapeutic window of an anti-SFRP1 monoclonal antibody (α-SFRP1) in double transgenic amyloid precursor protein (APP) and presenilin-1 (PS1) mice (APP/PS1).
methodsPharmacokinetics and target engagement of α-SFRP1 were assessed in groups of both male and female APP/PS1 mice using biotinylated or Zirconium-89 labeled (
resultsUsing DISCUSSION: Together, these findings demonstrate that SFRP1 remains a relevant therapeutic target in AD, but its effective modulation is constrained by limited brain exposure and a narrow therapeutic window, underscoring the importance of early intervention and prompting the search for improved brain-targeted delivery strategies.
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