ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2026
Dissecting Alzheimer's proteomic landscape through NULISA profiling of brain cell-specific extracellular vesicles.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
introductionBlood-based biomarkers are essential for early detection, monitoring, and therapeutic development in Alzheimer's disease (AD) and related dementia (ADRD), but current assays lack brain cell specificity and sensitivity to low-abundant proteins.
methodWe isolated the following brain cell-derived small extracellular vesicles (sEV) from the plasma of individuals with normal cognition (CN), mild cognitive impairment (MCI), or ADRD: neurons (NDE), astrocytes (ADE), microglia (MDE), oligodendrocytes (ODE), pericytes (PDE), and endothelial cells (EDE). Using NULISAseq, we profiled 122 proteins, spanning AD pathology, neurodegeneration, and neuroinflammation.
resultssEV proteomes showed distinct brain cell-type-specific signatures. MCI exhibited early dysregulation of neuroprotective, inflammatory, and vascular markers in NDE, MDE, and ODE. ADRD displayed broader alteration tau, amyloid, neuroinflammation, vascular dysfunction, and synaptic loss across multiple sEV populations. DISCUSSION: Combining NULISAseq with brain cell-derived plasma sEV enables the detection of multicellular molecular changes in ADRD, supporting their use as a minimally invasive platform for biomarker discovery.
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