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Open AccessJournal ArticleDOI

Biomarkers for Alzheimer's disease and other forms of dementia: clinical needs, limitations and future aspects.

Angel Cedazo-Minguez, +1 more
- 01 Jan 2010 - 
- Vol. 45, Iss: 1, pp 5-14
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TLDR
The present review summarizes the results achieved in the search for an early diagnosis of neurodegenerative disorders, and reflects the limitations and the perspectives of the field.
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This article is published in Experimental Gerontology.The article was published on 2010-01-01 and is currently open access. It has received 152 citations till now.

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Citations
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DTI measures in crossing-fibre areas: increased diffusion anisotropy reveals early white matter alteration in MCI and mild Alzheimer's disease.

TL;DR: Findings from a comprehensive study of diffusion tensor indices and probabilistic tractography obtained in a very large population of healthy controls, MCI and probable AD subjects emphasise the benefit of looking at the more complex regions in which spared and affected pathways are crossing to detect very early alterations of the white matter that could not be detected in regions consisting of one fibre population only.
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Identifying and validating biomarkers for Alzheimer's disease

TL;DR: It seems likely that only a combined analysis of several biomarkers will define a patient-specific signature to diagnose AD in the future.
Journal ArticleDOI

Identification of Altered Metabolic Pathways in Plasma and CSF in Mild Cognitive Impairment and Alzheimer’s Disease Using Metabolomics

TL;DR: Global metabolic changes in plasma and cerebrospinal fluid from the same individuals with different AD severity are determined and metabolomics could advance the understanding of the early disease mechanisms shared in progression from CN to MCI and to AD.
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Neurodegenerative diseases target large-scale human brain networks

TL;DR: To demonstrate multivariate network patterns of MRI gray matter that differentially affect Alzheimer’s disease, healthy aging and mild cognitive impairment.
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Proteomics of human cerebrospinal fluid: Discovery and verification of biomarker candidates in neurodegenerative diseases using quantitative proteomics

TL;DR: Some of the potential pitfalls in biomarker studies using CSF are focused on, the status of the field of CSF proteomics in general is summarized, and some of the most promising proteomics biomarker study approaches are discussed.
References
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Journal ArticleDOI

Mild Cognitive Impairment: Clinical Characterization and Outcome

TL;DR: Patients who meet the criteria for MCI can be differentiated from healthy control subjects and those with very mild AD, and appear to constitute a clinical entity that can be characterized for treatment interventions.
Journal ArticleDOI

Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging.

TL;DR: Recent studies examining spontaneous fluctuations in the blood oxygen level dependent (BOLD) signal of functional magnetic resonance imaging as a potentially important and revealing manifestation of spontaneous neuronal activity are reviewed.
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Frequently Asked Questions (15)
Q1. What are the contributions in "Biomarkers for alzheimer’s disease and other forms of dementia: clinical needs, limitations and future aspects" ?

Cedazo-Minguez et al. this paper proposed a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. 

An early diagnosis of Alzheimer’s disease (AD) and other types of dementia-causing disorders is vital in order to achieve effective treatments. 

It is also possible the presence of high intra- and inter-person variability due to factors that could influence the levels of a potential biomarker. 

Unbiased approaches have been pursued to evaluate a broad range of proteins (proteomics), small molecule metabolites (metabolomics), or transcripts (transcriptomics) in blood. 

However some considerations need to be taken into account when designing future studies, including the standardization of CSF extraction and the avoidance of factors like blood contamination, CSF gradient effects, and storage differences. 

Other proteins present in plasma with recently discovered associations to AD pathology have also been proposed as biomarkers, such ALZAS (ALZheimer ASsociated protein). 

the potential use of proteomic analysis of serum or plasma faces increased difficulties in assay standardization, and would require additional multilateral efforts. 

A model incorporating IL-6 receptor, cysteine, protein fraction α1 and cholesterol levels proved to be the best combination to discriminate AD from controls, although specificity to other cognitive disorders and PD was weaker (Teunissen and Scheltens, 2007). 

The estimated annual incidence of MCI in population studies is of about 2% in population studies (Larrieu et al., 2002; Palmer et al., 2008) and about 5–9% in clinical samples (Adak et al., 2004; de Leon et al., 2001). 

Mild cognitive impairment (MCI) is often, but not always, a transitional state between normal aging and dementia (Winblad et al., 2004). 

Another study of AD patients vs. controls identified a group of 20 candidate genes (from 3200 genes investigated) that showed an altered expression in AD (Kalman et al., 2005). 

The rates of transition between MCI and AD have been calculated between one-third to one-half for the MCIamnestic subtype (Palmer et al., 2008; Petersen et al., 1999) and two-thirds for MCImultidomains subtype over a period of three years. 

A 2-year longitudinal follow-up showed PIB not significant binding increase in AD patients despite declines in glucose metabolism and cognitive function (Engler et al., 2006). 

A multifactorial biomarker can be approached in two ways: a “knowledge-based” approach, incorporating “known” putative biomarkers (molecules with known association with the disease); or an unbiased survey of many hundreds or thousands of molecules. 

Elevated homocysteine is a risk factor for cardiovascular disease (Boushey et al., 1995) but its relation with AD risk is unknown.