Lead-exposure associated miRNAs in humans and Alzheimer’s disease as potential biomarkers of the disease and disease processes

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disease that eventually affects memory and behavior. The identification of biomarkers based on risk factors for AD provides insight into the disease since the exact cause of AD remains unknown. Several studies have proposed microRNAs (miRNAs) in blood as potential biomarkers for AD. Exposure to heavy metals is a potential risk factor for onset and development of AD. Blood cells of subjects that are exposed to lead detected in the circulatory system, potentially reflect molecular responses to this exposure that are similar to the response of neurons. In this study we analyzed blood cell-derived miRNAs derived from a general population as proxies of potentially AD-related mechanisms triggered by lead exposure. Subsequently, we analyzed these mechanisms in the brain tissue of AD subjects and controls. A total of four miRNAs were identified as lead exposure-associated with hsa-miR-3651, hsa-miR-150-5p and hsa-miR-664b-3p being negatively and hsa-miR-627 positively associated. In human brain derived from AD and AD control subjects all four miRNAs were detected. Moreover, two miRNAs (miR-3651, miR-664b-3p) showed significant differential expression in AD brains versus controls, in accordance with the change direction of lead exposure. The miRNAs’ gene targets were validated for expression in the human brain and were found enriched in AD-relevant pathways such as axon guidance. Moreover, we identified several AD relevant transcription factors such as CREB1 associated with the identified miRNAs. These findings suggest that the identified miRNAs are involved in the development of AD and might be useful in the development of new, less invasive biomarkers for monitoring of novel therapies or of processes involved in AD development.

Beyond CSF and Neuroimaging Assessment: Evaluating Plasma miR-145-5p as a Potential Biomarker for Mild Cognitive Impairment and Alzheimer’s Disease

“…These samples also came from the Institute Bor n -Bunge biobank and had a volume of 1 cm3 that was dissected with the same protocol and snap-frozen within 6 h after death. The detailed information on these samples is described in previous publications. , …”

“…The detailed information on these samples is described in previous publications. 83,84 CSF Biomarkers, MRI Biomarker, and MMSE Score. Lumbar puncture, subsequent CSF sampling, and further handling (including storage at −80 °C until analysis) were performed according to a previously described standard protocol.…”

The elusive role of herpesviruses in Alzheimer’s disease: current evidence and future directions

“…Dysregulated autophagy, which is associated with the progressive pathology of AD, has also been associated with neurotropic viruses [ 57 ]. While microRNAs (miRNAs) have been investigated as a potential biomarker of AD, viral infection may also contribute to the dysregulation of miRNA activity that has been linked to AD [ 58 , 59 ].…”

Investigating microRNAs as biomarkers in disorders of consciousness: a longitudinal multicenter study

“…Following TBI, a reduction in miRNA 16-5p levels has been observed both in plasma during the acute phase and in the brain of patients with fatal TBI 14 , 15 . Changes in 150-5p levels have been observed both in traumatic injuries and neurodegenerative diseases 16 , 17 . miRNA 132-3p and 23b-3p have been identified as regulators of inflammatory and apoptotic pathways implicated in HIBI and neurodegenerative diseases 18 – 20 .…”