Genetic Markers in Biological Fluids for Aging-Related Major Neurocognitive Disorder

Abstract

Aging-related major neurocognitive disorder (NCD), formerly named dementia, comprises of the different acquired diseases whose primary deficit is impairment in cognitive functions such as complex attention, executive function, learning and memory, language, perceptual/motor skills, and social cognition, and that are related to specific brain regions and/or networks. According to its etiology, the most common subtypes of major NCDs are due to Alzheimer’s disease (AD), vascular disease (VaD), Lewy body disease (LBD), and frontotemporal lobar degeneration (FTLD). These pathologies are frequently present in mixed forms, i.e., AD plus VaD or AD plus LBD, thus diagnosed as due to multiple etiologies. In this paper, the definitions, criteria, pathologies, subtypes and genetic markers for the most common age-related major NCD subtypes are summarized. The current diagnostic criteria consider cognitive decline leading to major NCD or dementia as a progressive degenerative process with an underlying neuropathology that begins before the manifestation of symptoms. Biomarkers associated with this asymptomatic phase are being developed as accurate risk factor and biomarker assessments are fundamental to provide timely treatment since no treatments to prevent or cure NCD yet exist. Biological fluid assessment represents a safer, cheaper and less invasive method compared to contrast imaging studies to predict NCD appearance. Genetic factors particularly have a key role not only in predicting development of the disease but also the age of onset as well as the presentation of comorbidities that may contribute to the disease pathology and trigger synergistic mechanisms which may, in turn, accelerate the neurodegenerative process and its resultant behavioral and functional disorders.

Potential fluid biomarkers for pathological brain changes in Alzheimer's disease: Implication for the screening of cognitive frailty

“…Several novel biomarkers associated with different aspects of AD neuropathology are being developed, including those related to synaptic dysfunction, neuronal damage and apoptosis, neuronal activity alteration, neuroinflammation, oxidative stress, metabolites, mitochondrial function and aberrant lipid metabolism. A bioinformatics approach for identifying specific single nucleotide polymorphisms ( 108 – 110 ) and epigenetic markers, including microRNAs ( 111 ) in the CSF or blood of patients with MCI, AD or non-AD dementia may also be useful for AD diagnosis and differentiation.…”

Serotonin 2 Receptors, Agomelatine, and Behavioral and Psychological Symptoms of Dementia in Alzheimer’s Disease

“…Some researchers have calculated that the number of dementia patients in China will reach 22 million by 2040. Among them, the proportion with AD is the highest, accounting for 60–70% of all dementias [ 13 ].…”

Autophagy Modulation in Aggresome Formation: Emerging Implications and Treatments of Alzheimer’s Disease

“…Alzheimer's disease (AD) is one of the most prevailing neurodegenerative diseases, characterized by memory dysfunction and the presence of hyperphosphorylated tau and amyloid β (Aβ) aggregates in multiple brain regions, including the hippocampus and cortex [18]. The clinical and pathological appearance of AD comprises memory impairment and slowness while performing normal regular activities [19]. The main pathological features represent intracellular aggregates composed of the extracellular deposition of amyloid-β (Aβ) and phosphorylated tau protein that form neurofibrillary tangles (NFTs) leading to the formation of senile plaques [20][21][22][23] (Figure 1).…”