Fig. 1 | Nature Communications

Fig. 1

From: Subtyping of circulating exosome-bound amyloid β reflects brain plaque deposition

Fig. 1

APEX platform for analysis of circulating exosome-bound Aβ. a Exosomes associate with Aβ proteins. Aβ proteins, the main component of amyloid plaques found in AD brain pathology, are released into the extracellular space. Exosomes are nanoscale extracellular membrane vesicles actively secreted by mammalian cells. Through their surface glycoproteins and glycolipids, exosomes can associate with the released Aβ proteins. b Transmission electron micrograph of exosome-bound Aβ. Exosomes derived from neuronal cells (SH-SY5Y) were treated with Aβ42 aggregates, and labeled with gold nanoparticles (10 nm) via a Aβ42-specific antibody. The nanoparticles appear as block dots (indicated by the red arrow). c APEX assay schematics. To enable sensitive profiling at the nanoscale, exosomes are first immuno-captured onto a plasmonic nanosensor (before amplification). Through an in situ enzymatic amplification, insoluble optical deposits are locally formed on the sensor-bound exosomes (after amplification). This deposition is spatially defined for molecular co-localization analysis, and changes the refractive index for SPR signal enhancement. To complement the enzymatic amplification, the nanosensor is back illuminated (away from the enzyme activity) to achieve analytical stability. The deposition causes a resultant red shift in the transmitted light through the nanosensor. d A representative schematic of changes in the transmission spectra with APEX amplification. Specific exosome binding (before) and subsequent amplification profiling (after) were monitored as transmission spectral shifts (Δλ) by the APEX platform. a.u., arbitrary unit. e Exosome-bound Aβ was measured using the APEX platform, in blood samples of patients with Alzheimer’s disease (AD), mild cognitive impairment (MCI), and controls with no cognitive impairment (NCI). The blood measurements were correlated to corresponding PET imaging of brain amyloid plaque deposition. f A photograph of the APEX microarray. Each sensor chip contains 6 × 10 sensing elements, made up of uniformly fabricated plasmonic lattice, for multiplexed measurements. See Supplementary Fig. 36 for sensor fabrication, characterization and design optimization, respectively

Back to article page