1. Plasma extracellular vesicles reveal early molecular differences in amyloid positive patients with early-onset mild cognitive impairment.
- Author
-
Cano, Amanda, Esteban-de-Antonio, Ester, Bernuz, Mireia, Puerta, Raquel, García-González, Pablo, de Rojas, Itziar, Olivé, Claudia, Pérez-Cordón, Alba, Montrreal, Laura, Núñez-Llaves, Raúl, Sotolongo-Grau, Óscar, Alarcón-Martín, Emilio, Valero, Sergi, Alegret, Montserrat, Martín, Elvira, Martino-Adami, Pamela V., Ettcheto, Miren, Camins, Antonio, Vivas, Assumpta, and Gomez-Chiari, Marta
- Subjects
- *
MILD cognitive impairment , *EXTRACELLULAR vesicles , *CEREBROSPINAL fluid examination , *CEREBRAL ventricles , *ALZHEIMER'S disease , *AMYLOID - Abstract
In the clinical course of Alzheimer's disease (AD) development, the dementia phase is commonly preceded by a prodromal AD phase, which is mainly characterized by reaching the highest levels of Aβ and p-tau-mediated neuronal injury and a mild cognitive impairment (MCI) clinical status. Because of that, most AD cases are diagnosed when neuronal damage is already established and irreversible. Therefore, a differential diagnosis of MCI causes in these prodromal stages is one of the greatest challenges for clinicians. Blood biomarkers are emerging as desirable tools for pre-screening purposes, but the current results are still being analyzed and much more data is needed to be implemented in clinical practice. Because of that, plasma extracellular vesicles (pEVs) are gaining popularity as a new source of biomarkers for the early stages of AD development. To identify an exosome proteomics signature linked to prodromal AD, we performed a cross-sectional study in a cohort of early-onset MCI (EOMCI) patients in which 184 biomarkers were measured in pEVs, cerebrospinal fluid (CSF), and plasma samples using multiplex PEA technology of Olink© proteomics. The obtained results showed that proteins measured in pEVs from EOMCI patients with established amyloidosis correlated with CSF p-tau181 levels, brain ventricle volume changes, brain hyperintensities, and MMSE scores. In addition, the correlations of pEVs proteins with different parameters distinguished between EOMCI Aβ(+) and Aβ(-) patients, whereas the CSF or plasma proteome did not. In conclusion, our findings suggest that pEVs may be able to provide information regarding the initial amyloidotic changes of AD. Circulating exosomes may acquire a pathological protein signature of AD before raw plasma, becoming potential biomarkers for identifying subjects at the earliest stages of AD development. Highlights: The pEVs proteome revealed early molecular differences between EOMCI Aβ(+) and Aβ(-) subjects. Olink© neurology proteins from pEVs of EOMCI Aβ(+) patients exhibited a strong negative correlation with CSF p-tau181. The levels of pEVs and CSF Olink© proteins correlated with CSF p-tau181 levels and age. Brain MRI characteristics of EOMCI Aβ(+) patients correlated with pEVs protein levels. pEVs biomarkers only linked early signs of inflammation to brain atrophy in EOMCI Aβ(+) individuals. The correlation of cognitive status and pEVs biomarkers differed between EOMCI Aβ(+) and Aβ(-) patients. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF