Abstract
Alzheimer’s disease (AD) is characterized as a complex, age-related neurological disorder of the human central nervous system (CNS) that involves the progressive mis-regulation of multiple biological pathways at multiple molecular, genetic, epigenetic, neurophysiological, cognitive, and behavioral levels. It has been about 8 years since the first reports of altered microRNA (miRNA) abundance and speciation: (i) in anatomical regions of the brain targeted by the AD process after post-mortem examination, (ii) in blood serum, and (iii) in cerebrospinal fluid (CSF) (1–3). Since then an in depth overview of the peer-reviewed literature has provided no general consensus of what miRNAs are up-or-down regulated in any tissue or biofluid compartment in thousands of AD patients. In this brief “Opinion” paper on “Biomarkers of Alzheimer’s disease: the present and the future,” we will highlight the extremely heterogeneous nature of miRNA expression in AD, based on very recent advances in the analysis of miRNA populations in various biofluid compartments compared to normally aging, neurologically normal controls. This work is based against a background of our laboratory’s 24 years of research experience into the structure and function of small, non-coding RNAs in the aging human CNS in health and in age-related neurological disease (4).
Highlights
Reviewed by: Cees Oudejans, VU University Medical Center Amsterdam, Netherlands Argonde Corien Van Harten, VU University Medical Center Amsterdam, Netherlands
Two laboratories have independently reported significant variation in the miRNA-34a-mediated triggering receptor expressed in myeloid/microglial cells-2 (TREM2) down-regulation in an African-American population that further underscores (i) the importance of investigating different ethnic populations for Alzheimer’s disease (AD) epigenetic risk; (ii) intrinsic variance and human biochemical and genetic individuality; and (iii) allelic heterogeneity and potentially diverse pathogenic contributory mechanisms to the AD process [9,10,11,12,13,14,15,16]
Related to these observations are studies that over the last 15 years have indicated that gene expression patterns at the messenger RNA level, Aβ peptide load, senile plaques (SP) and neurofibrillary tangles (NFT) densities and localization, and familial and clinical histories further underscore AD heterogeneity [8,9,10,11,12, 17,18,19,20]
Summary
Reviewed by: Cees Oudejans, VU University Medical Center Amsterdam, Netherlands Argonde Corien Van Harten, VU University Medical Center Amsterdam, Netherlands. Alzheimer’s disease (AD) is characterized as a complex, age-related neurological disorder of the human central nervous system (CNS) that involves the progressive mis-regulation of multiple biological pathways at multiple molecular, genetic, epigenetic, neurophysiological, cognitive, and behavioral levels.
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