Proteomic and biological profiling of extracellular vesicles from Alzheimer's disease human brain tissues

Abstract

Introduction Extracellular vesicles (EVs) from human Alzheimer's disease (AD) biospecimens contain amyloid beta (Aβ) peptide and tau. While AD EVs are known to affect brain disease pathobiology, their biochemical and molecular characterizations remain ill defined. Methods EVs were isolated from the cortical gray matter of 20 AD and 18 control brains. Tau and Aβ levels were measured by immunoassay. Differentially expressed EV proteins were assessed by quantitative proteomics and machine learning. Results Levels of pS396 tau and Aβ1–42 were significantly elevated in AD EVs. High levels of neuron‐ and glia‐specific factors are detected in control and AD EVs, respectively. Machine learning identified ANXA5, VGF, GPM6A, and ACTZ in AD EV compared to controls. They distinguished AD EVs from controls in the test sets with 88% accuracy. Discussion In addition to Aβ and tau, ANXA5, VGF, GPM6A, and ACTZ are new signature proteins in AD EVs.

Alzheimer’s disease progression characterized by alterations in the molecular profiles and biogenesis of brain extracellular vesicles

“…In line with these findings, an extensive review analysis of the CNS-derived EV literature in the context of AD is included in Table 2 and indicates that circulating neuronal EV contain Aβ1-42 up to 10 years prior to the clinical onset of AD [53]. Similarly, several studies demonstrate that circulating EV exert potential diagnostic/prognostic abilities in AD dementias [54][55][56][57][58]. Furthermore, the upregulated presence of phosphorylated Tau residues in circulating brain EV from cerebrospinal fluid was encountered in preclinical subjects with AD (Braak stage 3) [59].…”

The future of Extracellular Vesicles as Theranostics – an ISEV meeting report

“…cell disruption [10,13,14]. Although biofluids are the preferred source due to their accessibility and high abundance, tissue derived EVs harbour cell type specific information which can be utilized as valuable tools to report on the physiological and pathological conditions of organs [15][16][17][18][19].…”

Microglia-Derived Extracellular Vesicles Carrying miR-711 Alleviate Neurodegeneration in a Murine Alzheimer’s Disease Model by Binding to Itpkb

“…Abnormal hyperphosphorylation of Tau protein has already been manifested in AD associated with neurological deficits (Xia et al, 2017;Franzmeier et al, 2020). Meanwhile, research shows that EVs derived from AD brain samples can shed Tau protein (Muraoka et al, 2020). The aberrant Tau hyperphosphorylation in AD might be governed by treatment with EVs, thus impeding the progression of AD (Perrotte et al, 2020).…”