# Deficits of Alzheimer’s Disease Neuropsychological Architecture Correlate with Specific Exosomal mRNA Expression: Evidence of a Continuum?

## TL;DR

This study finds that specific exosomal mRNA patterns correlate with cognitive and functional deficits in Alzheimer's disease, suggesting potential for non-invasive diagnosis and treatment targets.

## Contribution

The study identifies novel and known AD-associated mRNAs linked to neuropsychological performance, revealing predictive relationships using PPS analysis.

## Key findings

- Exosomal mRNAs from genes like GABRB3, CADM1, SHROOM3, and SLC7A2 correlate with cognitive tests like MMSE and MoCA.
- PPS analysis shows non-linear and asymmetric associations between mRNA expression and neuropsychological variables.
- Findings suggest exosomal mRNA signatures could serve as biomarkers for AD diagnosis and monitoring.

## Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cognitive decline and complex molecular changes. Extracellular vesicles (EVs), particularly exosomes, play a key role in intercellular communication and disease progression, transporting proteins, lipids, and nucleic acids. While altered exosomal mRNA profiles have emerged as potential biomarkers for AD, the relationship between mRNA expression and AD neuropsychological deficits remains unclear. Here, we investigated the correlation between exosomx10-derived mRNA signatures and neuropsychological performance in a cohort from Barranquilla, Colombia. Expression profiles of 16,585 mRNAs in 15 AD patients and 15 healthy controls were analysed using Generalized Linear Models (GLMs) and the Predictive Power Score (PPS). We identified significant correlations between specific mRNA signatures and key neuropsychological variables, including the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Functional Assessment Screening Tool (FAST), Boston Naming Test, and Rey–Osterrieth Figure test. These mRNAs were in key AD-associated genes (i.e., GABRB3 and CADM1), while other genes are novel (i.e., SHROOM3, SLC7A2, GJB4, and XBP1). PPS analyses further revealed predictive relationships between mRNA expression and neuropsychological variables, accounting for non-linear patterns and asymmetric associations. If replicated in more extensive and heterogeneous studies, these findings provide critical insights into the molecular basis governing the natural history of AD, potential personalized and non-invasive diagnosis, prognosis, follow-up, and potential targets for future therapies.