Identification of novel biomarkers candidates for Alzheimer’s disease by bioinformatic analysis

Abstract

Alzheimer's disease (AD) is the most common form of dementia worldwide, above all characterized by the emergence of senile plaques (SPs) and neurofibrillary tangles (NFTs) in the patients' brains. These two deposits are the main histopathological hallmarks of AD, and even though these are characterized by main components, like amyloid fibrils in SPs and hyperphosphorylated Tau protein in NFTs, the molecular composition of these lesions is not yet fully understood. In this work, a bioinformatics analysis of the SPs and NFTs proteomes obtained by literature review was carried out. 836 proteins were obtained for SPs and 623 proteins for NFTs, with 374 representing the common proteome. Functional analysis (Gene Ontology) of the proteomes associated with each histopathological characteristic, allowed to identify the molecular events underlying the formation of these lesions. Additionally, the analysis of proteins common to the proteomes allowed to unravel pathways that link both histopathological events and identify putative molecular targets for AD diagnostic or therapeutic intervention.

A doença de Alzheimer (DA) é a forma de demência mais comum em todo o mundo, caracterizada sobretudo pelo aparecimento de placas senis (SPs) e tranças neurofibrilares (NFTs) no cérebro de pacientes. Estes dois depósitos são as principais características histopatológicas da DA e, embora sejam caracterizados por componentes principais, como fibrilas amilóides nas SPs e proteína Tau hiperfosforilada nas NFTs, a composição molecular destas lesões ainda não está totalmente desvendada. Neste trabalho, procedeu-se a uma análise bioinformática dos proteomas das SPs e das NFTs obtidos por revisão da literatura. Obtiveram-se 836 proteínas para as SPs e 623 proteínas para as NFTs, sendo que 374, representam o proteoma comum. Análise funcional (Gene Ontology) dos proteomas associados a cada característica histopatológica, permitiu identificar os eventos moleculares subjacentes à formação destas lesões. Adicionalmente, a análise das proteínas comuns aos proteomas permitiu desvendar vias que ligam ambos os eventos histopatológicos e identificar novos alvos moleculares putativos para diagnóstico de DA ou intervenção terapêutica.