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      Lipidomics and proteomics: An integrative approach for early diagnosis of dementia and Alzheimer’s disease

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          Abstract

          Alzheimer’s disease (AD) is the most common neurodegenerative disorder and considered to be responsible for majority of worldwide prevalent dementia cases. The number of patients suffering from dementia are estimated to increase up to 115.4 million cases worldwide in 2050. Hence, AD is contemplated to be one of the major healthcare challenge in current era. This disorder is characterized by impairment in various signaling molecules at cellular and nuclear level including aggregation of Aβ protein, tau hyper phosphorylation altered lipid metabolism, metabolites dysregulation, protein intensity alteration etc. Being heterogeneous and multifactorial in nature, the disease do not has any cure or any confirmed diagnosis before the onset of clinical manifestations. Hence, there is a requisite for early diagnosis of AD in order to downturn the progression/risk of the disorder and utilization of newer technologies developed in this field are aimed to provide an extraordinary assistance towards the same. The lipidomics and proteomics constitute large scale study of cellular lipids and proteomes in biological matrices at normal stage or any stage of a disease. The study involves high throughput quantification and detection techniques such as mass spectrometry, liquid chromatography, nuclear mass resonance spectroscopy, fluorescence spectroscopy etc. The early detection of altered levels of lipids and proteins in blood or any other biological matrices could aid in preventing the progression of AD and dementia. Therefore, the present review is designed to focus on the recent techniques and early diagnostic criteria for AD, revealing the role of lipids and proteins in this disease and their assessment through different techniques.

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          Most cited references122

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          Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease.

          The pathophysiological process of Alzheimer's disease (AD) is thought to begin many years before the diagnosis of AD dementia. This long "preclinical" phase of AD would provide a critical opportunity for therapeutic intervention; however, we need to further elucidate the link between the pathological cascade of AD and the emergence of clinical symptoms. The National Institute on Aging and the Alzheimer's Association convened an international workgroup to review the biomarker, epidemiological, and neuropsychological evidence, and to develop recommendations to determine the factors which best predict the risk of progression from "normal" cognition to mild cognitive impairment and AD dementia. We propose a conceptual framework and operational research criteria, based on the prevailing scientific evidence to date, to test and refine these models with longitudinal clinical research studies. These recommendations are solely intended for research purposes and do not have any clinical implications at this time. It is hoped that these recommendations will provide a common rubric to advance the study of preclinical AD, and ultimately, aid the field in moving toward earlier intervention at a stage of AD when some disease-modifying therapies may be most efficacious. Copyright © 2011. Published by Elsevier Inc.
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            Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing

            Risk for late-onset Alzheimer's disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large genome-wide association meta-analysis of clinically diagnosed LOAD (94,437 individuals). We confirm 20 previous LOAD risk loci and identify five new genome-wide loci (IQCK, ACE, ADAM10, ADAMTS1, and WWOX), two of which (ADAM10, ACE) were identified in a recent genome-wide association (GWAS)-by-familial-proxy of Alzheimer's or dementia. Fine-mapping of the human leukocyte antigen (HLA) region confirms the neurological and immune-mediated disease haplotype HLA-DR15 as a risk factor for LOAD. Pathway analysis implicates immunity, lipid metabolism, tau binding proteins, and amyloid precursor protein (APP) metabolism, showing that genetic variants affecting APP and Aβ processing are associated not only with early-onset autosomal dominant Alzheimer's disease but also with LOAD. Analyses of risk genes and pathways show enrichment for rare variants (P = 1.32 × 10-7), indicating that additional rare variants remain to be identified. We also identify important genetic correlations between LOAD and traits such as family history of dementia and education.
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              Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer’s disease risk

              Alzheimer's disease (AD) is highly heritable and recent studies have identified over 20 disease-associated genomic loci. Yet these only explain a small proportion of the genetic variance, indicating that undiscovered loci remain. Here, we performed a large genome-wide association study of clinically diagnosed AD and AD-by-proxy (71,880 cases, 383,378 controls). AD-by-proxy, based on parental diagnoses, showed strong genetic correlation with AD (rg = 0.81). Meta-analysis identified 29 risk loci, implicating 215 potential causative genes. Associated genes are strongly expressed in immune-related tissues and cell types (spleen, liver, and microglia). Gene-set analyses indicate biological mechanisms involved in lipid-related processes and degradation of amyloid precursor proteins. We show strong genetic correlations with multiple health-related outcomes, and Mendelian randomization results suggest a protective effect of cognitive ability on AD risk. These results are a step forward in identifying the genetic factors that contribute to AD risk and add novel insights into the neurobiology of AD.
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                Author and article information

                Contributors
                Journal
                Front Genet
                Front Genet
                Front. Genet.
                Frontiers in Genetics
                Frontiers Media S.A.
                1664-8021
                09 February 2023
                2023
                : 14
                : 1057068
                Affiliations
                [1] 1 Division of Neuroscience and Ageing Biology , CSIR- Central Drug Research Institute , Lucknow, India
                [2] 2 Academy of Scientific and Innovative Research (AcSIR) , Ghaziabad, India
                Author notes

                Edited by: Prachi Srivastava, Amity University, India

                Reviewed by: Kaushik Kumar Dey, St. Jude Children’s Research Hospital, United States

                Ian James Martins, University of Western Australia, Australia

                *Correspondence: Shubha Shukla, shubha_shukla@ 123456cdri.res.in

                This article was submitted to Neurogenomics, a section of the journal Frontiers in Genetics

                Article
                1057068
                10.3389/fgene.2023.1057068
                9946989
                36845373
                77091a12-9c70-4589-9d60-19030420ba3e
                Copyright © 2023 Tiwari and Shukla.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 29 September 2022
                : 23 January 2023
                Categories
                Genetics
                Review

                Genetics
                alzheimer’s disease,lipidomics,proteomics,diagnosis,high throughput techniques
                Genetics
                alzheimer’s disease, lipidomics, proteomics, diagnosis, high throughput techniques

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