Recent Evidence in Epigenomics and Proteomics Biomarkers for Early and Minimally Invasive Diagnosis of Alzheimer’s and Parkinson’s Diseases

Abstract

Background: Alzheimer’s (AD) and Parkinson’s diseases (PD) show deposits of improperly folded modified proteins, so protein expression mechanisms are involved since early stages. Several studies evaluated epigenomics and proteomics profiles in these patients, with promising results. In general, they focused on early, specific, and minimally invasive biomarkers for diagnosis and prognosis of AD and PD. Objectives: This review aimed at summarizing results to find the most reliable evidence in the field. Method: A PubMed search was carried out. It was limited to the last 6 years, using a combination of search terms related to AD, PD and epigenetics or proteomics. Results: Among epigenomics studies, most of them focused on microRNAs (miRNAs) as candidate diagnosis biomarkers for AD or PD from blood samples like miR-342-3p, miR-107, miR-106a-5p, miR-106b-5p, miR-195, and miR-19b. In addition, the DNA methylation has been tested in a few works, obtaining significant differences in some genes (NCAPH2/LMF2 COASY, SPINT1, BDNFTREM1, TREM2, NPAS2, PDE4D), which could be useful for evaluating the disease progression as well as potential risk factors. Regarding proteomics, most of the studies were untargeted and used plasma or serum samples. In general, they highlighted the importance of coagulation, inflammation pathways, and oxidative stress. Among targeted studies, some proteins (phosphorylated tau, C reactive protein (CRP), interleukins, necrosis factors, transferrin, glial fibrillary acidic protein (GFAP),and neurofilaments) showed different plasma levels in AD and PD patients in comparison with healthy participants. Finally, a few studies have identified specific-AD and PD epigenetic and proteomic biomarkers (ApoE and oxidized DJ-1) in comparison with other similar pathologies. Conclusion: In general, there is a common lack of clinical validation of these potential biomarkers, for which its use in the clinical practice is still limited.

A Transcriptome Analysis of mRNAs and Long Non-Coding RNAs in Patients with Parkinson’s Disease

“…Our study had different objectives, through the analysis of the transcriptome, but it certainly provides results that could be the basis of interesting future studies aimed at large-scale, numerical validation of what has been observed and, therefore, that could further confirm our findings. An emerging problem in the literature is the growing evidence in the field of proteomics in these pathologies, but studies are still few [82].…”

MicroRNA-668-3p regulates oxidative stress and cell damage induced by Aβ1-42 by targeting the OXR1/p53-p21 axis

“…For example, recent studies have shown that low levels of miRNAs miR-27a-3p ( 43 ) and high levels of miR-483-3p ( 44 ) can promote the development of AD. Moreover, miR-342-3p ( 45 ) and miR-103a-3p ( 46 ) affect the occurrence and subsequent stages of AD. The purpose of our study was to clarify the mechanisms underlying AD development by screening for miRNAs that affect AD progression.…”

Advances in human brain proteomics analysis of neurodegenerative diseases

“…Among them, several proteins were associated with synaptic structures, including downregulated (caskin-1, TMEM163 and REEP2) and upregulated (δ2-catenin, AHA-1, PHYHIPL and α-1-syntrophin) proteins, suggesting that hippocampal synaptic dysfunction plays a role in PD. However, minimally invasive samples (i.e., serum and plasma samples) are predominantly used to evaluate proteome profiles in PD, with the results highlighting the importance of coagulation, inflammation, and oxidative stress pathways (Mayo, Benito-León, Peña-Bautista, Baquero, & Cháfer-Pericás, 2021). In addition, in comparison with healthy participants, PD patients showed differences in the levels of some proteins, such as CRP, interleukins, necrosis factors, transferrin, glia fibrillary acidic protein (GFAP), neurofilament proteins, Rab35, ApoA1, and DJ-1.…”