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      The Association Between Plasma α-Synuclein (α-syn) Protein, Urinary Alzheimer-Associated Neuronal Thread Protein (AD7c-NTP), and Apolipoprotein Epsilon 4 (ApoE ɛ4) Alleles and Cognitive Decline in 60 Patients with Alzheimer’s Disease Compared with 28 Age-Matched Normal Individuals

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          Abstract

          Background

          Accumulating evidence has shown that α-synuclein (α-syn) pathology is involved in the pathophysiology of Alzheimer’s disease (AD). This study aimed to investigate the association between the levels of plasma α-syn protein, urinary Alzheimer-associated neuronal thread protein (AD7c-NTP), apolipoprotein epsilon 4 (ApoE ɛ4) alleles and cognitive decline in 60 AD patients compared with 28 age-matched normal controls (NCs) at a single center.

          Material/Methods

          All participants underwent α-syn, apolipoprotein E (ApoE), AD7c-NTP, cholesterol (CHO), high-density lipoprotein (HDL), low-density lipoprotein (LDL) and triglycerides (TGs) analyses, neuropsychological scale assessments and neuroimaging analysis. Moreover, urine and peripheral blood samples were collected from all participants. The levels of plasma α-syn and AD7c-NTP were assayed using an enzyme-linked immunosorbent assay (ELISA) kit. Other test results were obtained from China-Japan Friendship Hospital.

          Results

          We found that plasma α-syn levels were significantly different between AD patients and NCs ( p=0.045). α-Syn levels were also associated with AD7c-NTP (r=0.231, p=0.03) but not ApoE ɛ4 (Z=−0.147, p=0.883) levels. Neither α-syn [CHO ( p=0.432), HDL ( p=0.484), LDL ( p=0.733) or TGs ( p=0.253)] nor AD7c-NTP [CHO ( p=0.867), HDL ( p=0.13), LDL ( p=0.57) or TGs ( p=0.678)] had a relationship with lipids.

          Conclusions

          This study showed that the levels of plasma α-syn protein and urinary AD7c-NTP were significantly increased in AD patients compared with NCs, but not with ApoE alleles or serum lipid levels.

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          Most cited references49

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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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            Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families.

            The apolipoprotein E type 4 allele (APOE-epsilon 4) is genetically associated with the common late onset familial and sporadic forms of Alzheimer's disease (AD). Risk for AD increased from 20% to 90% and mean age at onset decreased from 84 to 68 years with increasing number of APOE-epsilon 4 alleles in 42 families with late onset AD. Thus APOE-epsilon 4 gene dose is a major risk factor for late onset AD and, in these families, homozygosity for APOE-epsilon 4 was virtually sufficient to cause AD by age 80.
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              Alzheimer's disease.

              Although the prevalence of dementia continues to increase worldwide, incidence in the western world might have decreased as a result of better vascular care and improved brain health. Alzheimer's disease, the most prevalent cause of dementia, is still defined by the combined presence of amyloid and tau, but researchers are gradually moving away from the simple assumption of linear causality as proposed in the original amyloid hypothesis. Age-related, protective, and disease-promoting factors probably interact with the core mechanisms of the disease. Amyloid β42, and tau proteins are established core cerebrospinal biomarkers; novel candidate biomarkers include amyloid β oligomers and synaptic markers. MRI and fluorodeoxyglucose PET are established imaging techniques for diagnosis of Alzheimer's disease. Amyloid PET is gaining traction in the clinical arena, but validity and cost-effectiveness remain to be established. Tau PET might offer new insights and be of great help in differential diagnosis and selection of patients for trials. In the search for understanding the disease mechanism and keys to treatment, research is moving increasingly into the earliest phase of disease. Preclinical Alzheimer's disease is defined as biomarker evidence of Alzheimer's pathological changes in cognitively healthy individuals. Patients with subjective cognitive decline have been identified as a useful population in whom to look for preclinical Alzheimer's disease. Moderately positive results for interventions targeting several lifestyle factors in non-demented elderly patients and moderately positive interim results for lowering amyloid in pre-dementia Alzheimer's disease suggest that, ultimately, there will be a future in which specific anti-Alzheimer's therapy will be combined with lifestyle interventions targeting general brain health to jointly combat the disease. In this Seminar, we discuss the main developments in Alzheimer's research.
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                Author and article information

                Journal
                Med Sci Monit
                Med Sci Monit
                Medical Science Monitor
                Medical Science Monitor : International Medical Journal of Experimental and Clinical Research
                International Scientific Literature, Inc.
                1234-1010
                1643-3750
                2021
                27 July 2021
                16 July 2021
                : 27
                : e932998-1-e932998-9
                Affiliations
                [1 ]Department of Neurology, Peking University China-Japan Friendship School of Clinical Medicine, Beijing, PR China
                [2 ]Department of Neurology, China-Japan Friendship Hospital, Beijing, PR China
                [3 ]Department of Neurology, Graduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, PR China
                [4 ]Department of Cardiovascular, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, PR China
                Author notes
                Corresponding Author: Dantao Peng, e-mail: pengdantao2000@ 123456163.com
                [A]

                Study Design

                [B]

                Data Collection

                [C]

                Statistical Analysis

                [D]

                Data Interpretation

                [E]

                Manuscript Preparation

                [F]

                Literature Search

                [G]

                Funds Collection

                [*]

                Shuang Lv and Xiao Zhou contributed equally to this work

                Article
                932998
                10.12659/MSM.932998
                8325392
                34312362
                ca4c7dcf-b070-4a6e-95d4-58ba924f4919
                © Med Sci Monit, 2021

                This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International ( CC BY-NC-ND 4.0)

                History
                : 04 May 2021
                : 11 July 2021
                Categories
                Clinical Research

                ad7c-ntp protein, human,alpha-synuclein,alzheimer disease,apolipoprotein e4

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