The Role of Clinical Proteomics, Lipidomics, and Genomics in the Diagnosis of Alzheimer’s Disease

Abstract

The early diagnosis of Alzheimer’s disease (AD) has become important to the reversal and treatment of neurodegeneration, which may be relevant to premature brain aging that is associated with chronic disease progression. Clinical proteomics allows the detection of various proteins in fluids such as the urine, plasma, and cerebrospinal fluid for the diagnosis of AD. Interest in lipidomics has accelerated with plasma testing for various lipid biomarkers that may with clinical proteomics provide a more reproducible diagnosis for early brain aging that is connected to other chronic diseases. The combination of proteomics with lipidomics may decrease the biological variability between studies and provide reproducible results that detect a community’s susceptibility to AD. The diagnosis of chronic disease associated with AD that now involves genomics may provide increased sensitivity to avoid inadvertent errors related to plasma versus cerebrospinal fluid testing by proteomics and lipidomics that identify new disease biomarkers in body fluids, cells, and tissues. The diagnosis of AD by various plasma biomarkers with clinical proteomics may now require the involvement of lipidomics and genomics to provide interpretation of proteomic results from various laboratories around the world.

Single Gene Inactivation with Implications to Diabetes and Multiple Organ Dysfunction Syndrome

“…Sirt 1 repression induces mitophagy with the development of MODS and may supersede the connections between diabetic genes (Type 1 and 2) and their associated diseases (Figure 2). Sirt 1 plays an important role in the regulation fibroblast growth factor 21 [82][83][84] and the apelinergic pathway [85] with connections to brain insulin resistance (stroke, dementia, AD) [86]. In Type 2 diabetes the relevance of stress, anxiety and hyperphagia are associated with defective apelinergic pathways [85] and severity of diabetes (post-transcriptional defect) associated with Sirt 1-apelinergic system defects in mental disorders [87].…”

Heat Shock Gene Sirtuin 1 Regulates Post-Prandial Lipid Metabolism with Relevance to Nutrition and Appetite Regulation in Diabetes

“…FGF21 therapy [42,43] in Type 2 and Type 3 diabetes may be ineffective with the development of cardiac ageing with relevance to core body temperature regulation that is determined by mi-34a/Sirt 1 gene expression with low adiponectin levels [36,44] (Figure 2). Healthy diets that maintain Sirt 1 activity in the brain and liver have become important to many diabetics in the developing and developed world with relevance to food technology that involve the hepatic metabolism of bacterial lipopolysaccharides (LPS) that has become important to the reversal of Type 2 diabetes and Type 3 diabetes [45,46].…”

“…In the developing and developed world diabetic treatment has become important with defective Sirt 1 gene expression determined by miR-34a [18,36] related to defective cell proliferation in the brain and the liver ( Figure 2). Defective thermoregulation may be relevant to ingestion of food (Sirt 1 defective)with inappropriate post-prandial lipid and amyloid beta metabolism that inactivate magnesium therapy that may now be relevant to HSP and amyloid beta metabolism with relevance to myocardial infarction [3,37].…”

“…Sirt 1 regulation of cell senescence in diabetes involves cell ontogeny with transcriptional ontogeny defective via the transcriptional factor p53 involved in the regulation of various other anti-aging genes [30][31][32][33][34][35] such as klotho, p66shc, FOXO3a, micro RNA 34a [18] and transcription factors involve post-prandial lipid metabolism, metabolic activity, insulin resistance, cellular ontogeny, inflammation and xenobiotic metabolism [18,36] (Figure 2). In the developing and developed world diabetic treatment has become important with defective Sirt 1 gene expression determined by miR-34a [18,36] related to defective cell proliferation in the brain and the liver ( Figure 2).…”

Magnesium Therapy Prevents Senescence with the Reversal of Diabetes and Alzheimer’s Disease

“…Magnesium therapy now involves the use of various products that stimulate the absorption of magnesium into the blood and magnesium supplementation has been introduced to manage insulin resistance, NAFLD and cardiovascular disease [192] [193]. Magnesium dysfunction induces Type 3 diabetes [15] [16] with brain insulin resistance (Figure 3) closely connected to magnesium levels (Sirt1 regulation), glucose dyshomeostasis, LPS induced repression of Sirt1 [194] with relevance to Aβ oligomer formation. High fibre diets that contain short chain fatty acids [195] [196] have been shown to stimulate magnesium absorption with relevance to management of insulin resistance and NAFLD.…”