Epigenetic Peripheral Biomarkers for Early Diagnosis of Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and represents the leading cause of cognitive impairment and dementia in older individuals throughout the world. The main hallmarks of AD include brain atrophy, extracellular deposition of insoluble amyloid-β (Aβ) plaques, and the intracellular aggregation of protein tau in neurofibrillary tangles. These pathological modifications start many years prior to clinical manifestations of disease and the spectrum of AD progresses along a continuum from preclinical to clinical phases. Therefore, identifying specific biomarkers for detecting AD at early stages greatly improves clinical management. However, stable and non-invasive biomarkers are not currently available for the early detection of the disease. In the search for more reliable biomarkers, epigenetic mechanisms, able to mediate the interaction between the genome and the environment, are emerging as important players in AD pathogenesis. Herein, we discuss altered epigenetic signatures in blood as potential peripheral biomarkers for the early detection of AD in order to help diagnosis and improve therapy.

Circulating Non-Coding RNAs as Potential Diagnostic Biomarkers in Hepatocellular Carcinoma

“…This method allows evaluation of the expression of a few specific molecules but do not permit the discovery of new ncRNAs or provide an overview of all ncRNAs. 21 RNA-sequencing is a high-throughput sequencing method which can be used to sequence the entire transcriptome, leading to the identification of new ncRNAs. 22 Microarray-based technique is another powerful high-throughput method extensively used for ncRNA profiling, because of their ability to screen large number of ncRNAs simultaneously in large variety of samples.…”

“…This method allows evaluation of the expression of a few specific molecules but do not permit the discovery of new ncRNAs or provide an overview of all ncRNAs. 21 …”

Natural Bioactive Products as Epigenetic Modulators for Treating Neurodegenerative Disorders

“…Other examples of hypermethylated genes are thromboxane A2 receptor ( TBXA2R ), sorbin, SH3 domain-containing 3 ( SORBS3 ), and spectrin beta 4 ( SPTBN4 ), which are hypermethylated in animal models of AD and in patients with AD [ 46 ]. Thus, blood DNA methylation has been proposed as a biomarker for dementia [ 38 , 39 , 41 , 47 , 48 ].…”

Linking the Amyloid, Tau, and Mitochondrial Hypotheses of Alzheimer’s Disease and Identifying Promising Drug Targets

“…Given that epigenetic and mitoepigenetic changes can be detected even in the periphery, they have the potential to be included in the list of AD risk factors and biomarkers and to become therapeutic targets for new drugs. The epigenetics of AD, including epigenetic modulation by microRNAs, and possible treatment opportunities have been described and discussed in detail in a number of reviews [ 83 , 84 , 85 , 86 , 87 , 88 , 89 ].…”