A parallel-serial DNA nanodevice enables multichannel decoding of the BACE1-AS1/BACE1 axis in Alzheimer’s disease
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A parallel serial DNA nanodevice is built for multichannel decoding of the BACE1-AS1/BACE1 axis.
Relying on a hexagram DNA scaffold, the device produces coordinated fluorescence signals to show distinct molecular states.
This biosensor obtains LODs of 0.16 nM for BACE1 and 0.56 nM for BACE1-AS1.
SHapley Additive exPlanations (SHAP) analysis identifies BACE1-AS1 as a more influential biomarker for AD diagnostic discrimination.
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ABSTRACT
The accurate decoding of molecular interactions within disease-related signaling pathways remains a critical challenge for early and reliable diagnosis of Alzheimer’s disease (AD). While individual biomarkers such as BACE1 and its antisense transcript BACE1-AS1 have been widely studied, their coupled behavior within a functional axis proves difficult to interpret via single-output biosensing strategies. Here, we report a parallel–serial DNA nanodevice that translates the combined profile of the BACE1-AS1/BACE1 axis into multichannel fluorescence outputs. Built upon a hexagram DNA scaffold, the nanodevice generates distinct cleavage patterns in response to BACE1, BACE1-AS1, or their coexistence; these structural changes further convert into programmable downstream logic operations. Unlike conventional AND or OR logic gates that yield a single binary signal, this design combines parallel recognition with serial validation, generating three coordinated fluorescence readouts that reflect different pathway states. Results show that the device achieves limits of detection (LODs) of 0.16 nM and 0.56 nM for BACE1 and BACE1-AS1, respectively. Integration of multichannel outputs with machine learning (ML) models enables accurate discrimination of AD samples from healthy controls. Feature attribution analysis further reveals that BACE1-AS1 exerts a stronger influence on diagnostic classification than BACE1. By coupling DNA logic with multichannel signal cooperation, this work establishes a feasible strategy to convert molecular input signals into pathway-level characterizations and clinically interpretable readouts for AD detection. -
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REFERENCES
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Cheng T., Yu J., Zhou H., et al. (2026). A parallel-serial DNA nanodevice enables multichannel decoding of the BACE1-AS1/BACE1 axis in Alzheimer’s disease. The Innovation Neurology 1:100005. https://doi.org/10.59717/j.xinn-tine.2026.100005
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Cheng T., Yu J., Zhou H., et al. (2026). A parallel-serial DNA nanodevice enables multichannel decoding of the BACE1-AS1/BACE1 axis in Alzheimer’s disease. The Innovation Neurology 1:100005. https://doi.org/10.59717/j.xinn-tine.2026.100005
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Figure 1.
Schematic illustration of machine learning-enhanced parallel-serial DNA nanodevice (PSDN) for multidimensional dissection of the BACE-AS1/BACE1 axis
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Figure 2.
Feasibility validation of the PSDN biosensor for BACE1-AS1/BACE1 sensing
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Figure 3.
Systematic optimization of the conditions of the PSDN biosensor
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Figure 4.
Performance of the PSDN biosensor in the FAM channel
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Figure 5.
Performance of the PSDN biosensor in the TAMRA and Cy5 channel
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Figure 6.
Machine learning-assisted PSDN platform for AD diagnosis
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Figure 7.
Gene importance and pathway status assessment of the PSDN platform
