2013
DOI: 10.1590/1516-4446-2012-3505
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Abstract: Objective: To present a critical review of publications reporting on the rationale and clinical implications of the use of biomarkers for the early diagnosis of Alzheimer's disease (AD). Methods: We conducted a systematic search of the PubMed and Web of Science electronic databases, limited to articles published in English between 1999 and 2012, and based on the following terms: mild cognitive impairment, Alzheimer's disease OR dementia, biomarkers. We retrieved 1,130 articles, of which 175 were reviews. Overa… Show more

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Cited by 19 publications
(172 citation statements)
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References 142 publications
(172 reference statements)
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“…Alzheimer's dementia (AD) usually progresses slowly for a decade or more before a diagnosis of dementia, and a mild cognitive impairment (MCI) is proposed to capture the prodromal stages of various etiologies of dementia, including AD. To date, molecular, functional, and structural biomarkers have been developed to accurately diagnose AD (Ishii, ) and to predict conversion from MCI to AD at an early time (Forlenza, Diniz, Teixeira, Stella, & Gattaz, ). Among these biomarkers, structural MRI is indispensable, and atrophy of the medial temporal lobe including the hippocampus is considered as a valid diagnostic marker (Frisoni, Fox, Jack, Scheltens, & Thompson, ) and as a risk factor of conversion to AD (Grundman et al., ).…”
Section: Introductionmentioning
confidence: 99%
“…Alzheimer's dementia (AD) usually progresses slowly for a decade or more before a diagnosis of dementia, and a mild cognitive impairment (MCI) is proposed to capture the prodromal stages of various etiologies of dementia, including AD. To date, molecular, functional, and structural biomarkers have been developed to accurately diagnose AD (Ishii, ) and to predict conversion from MCI to AD at an early time (Forlenza, Diniz, Teixeira, Stella, & Gattaz, ). Among these biomarkers, structural MRI is indispensable, and atrophy of the medial temporal lobe including the hippocampus is considered as a valid diagnostic marker (Frisoni, Fox, Jack, Scheltens, & Thompson, ) and as a risk factor of conversion to AD (Grundman et al., ).…”
Section: Introductionmentioning
confidence: 99%
“…Tau is normally associated to microtubules in neurons, however in AD brains the protein becomes hyperphosphorylated leading to protein aggregation [35]. These two pathological changes are reflected in CSF and can be measured as low levels of the A␤42 peptide and increased levels of total and phoshorylated tau [36]. Reports suggest that amyloid plaques represent the initial pathological process, which is followed by neuronal injury [37].…”
Section: Alzheimer's Diseasementioning
confidence: 99%
“…Potential neuroimaging techniques that can improve the accuracy to predict conversion to AD are considered as well as potential CSF, urine, blood and genetic biomarkers of AD (continuation). risk factor to MCI conversion to AD (45) associated with the risk of incident AD and dementia (51) and suitable in normal cognitive status conversion to MCI or AD (54,55) associated with higher risk of incident AD and dementia (51) lack of correlation between plasma Aβ levels and plasma homocysteine (50) and Aβ-42 levels in CSF and plasma (57,58) suitable to predict conversion to AD (sensitivity 80% and specificity 82%) (59) strongest correlations in MCI patients (60) strong correlations with oxidized lipoprotein receptor-related protein-1 (sLRP), CSF tau / Aβ-42 ratios and reductions in MMSE scores, risk of MCI and AD (81) correlation with cognitive function (62) useful tool to predict MCI conversion to AD (45,49,50,(63)(64)(65)70) reliable biochemical marker in early stages of AD and in the discrimination from other types of dementia (sensibility 87% and specificity 82%) (66) risk marker for AD in subjects with MCI (67) useful in prediction of incident impairment in asymptomatic individuals (68) predictive of cognitive decline and hippocampal volume loss (69) candidate biomarkers for AD and the predementia condition of MCI (73) related to familial AD (prevalence around 0,1%) (45) risk factor for AD (45) risk factor for sporadic AD (45) involved in familial AD and other neurodegenerative diseaes (80,81) (myo-inositol/creatine ratio) in the cortical area of right parietal lobe in MCI subjects predicted the conversion to AD with sensitivity 70% and specificity 85%.…”
Section: Challenges In the Discovery Of Potential Biomarkers In Alzhementioning
confidence: 99%
“…Panels of serum biomarkers for inflammation, homocysteine and cholesterol metabolism and brain specific proteins have been evaluated, yielding high accuracy, close to 90%, to differentiate AD patients from control cases and they also provided a useful tool to predict MCI patients that later converted to AD patients 50 . As an example, some identified plasma biomarkers are α2-macroglobulin, complement factor H, homocysteine, cholesterol, E4 isoform of apolipoprotein E, F2-isoprostanes, Aβ autoantibodies, apolipoprotein A1, clusterin/apolipoprotein-J, isoprostane or glycogen synthase kinase (GSK-3β) 45,[63][64][65] . Regarding calmodulin, this potential plasma biomarker was found significantly upregulated in MCI and AD patients with a sensitivity of 0.87 and a specificity of 0.82, suggesting its possible role in the identification of early stages in AD and in the discrimination from other types of dementia 66 .…”
Section: The Search For Reliable Blood-based Biomarkersmentioning
confidence: 99%