Diagnosis-Independent Alzheimer Disease Biomarker Signature in Cognitively Normal Elderly People

Meyer, Geert De; Shapiro, F.L.; Vanderstichele, Hugo; Vanmechelen, Eugeen; Engelborghs, Sebastiaan; Deyn, Peter Paul De; Coart, Els; Hansson, Oskar; Minthon, Lennart; Zetterberg, Henrik; Blennow, Kaj; Shaw, Leslie M.; Trojanowski, John Q.

doi:10.1001/archneurol.2010.179

Cited by 398 publications

(275 citation statements)

References 25 publications

(42 reference statements)

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“…The plots per subgroup show that EC variability against test score is lower in e4 carriers. This indicates differences in brain network organization between carriers and noncarriers that make the brain more vulnerable to AD‐related pathology (De Meyer et al., 2010; Evans et al., 2014; Mintun et al., 2006; Sperling et al., 2011). In an important way, this does not lead to decreased cognitive decline or visuoperceptual performance.…”

Section: Discussionmentioning

confidence: 99%

Functional brain network centrality is related to APOE genotype in cognitively normal elderly

et al. 2018

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IntroductionAmyloid plaque deposition in the brain is an early pathological change in Alzheimer's disease (AD), causing disrupted synaptic connections. Brain network disruptions in AD have been demonstrated with eigenvector centrality (EC), a measure that identifies central regions within networks. Carrying an apolipoprotein (APOE)‐ε4 allele is a genetic risk for AD, associated with increased amyloid deposition. We studied whether APOE‐ε4 carriership is associated with EC disruptions in cognitively normal individuals.MethodsA total of 261 healthy middle‐aged to older adults (mean age 56.6 years) were divided into high‐risk (APOE‐ε4 carriers) and low‐risk (noncarriers) groups. EC was computed from resting‐state functional MRI data. Clusters of between‐group differences were assessed with a permutation‐based method. Correlations between cluster mean EC with brain volume, CSF biomarkers, and psychological test scores were assessed.ResultsDecreased EC in the visual cortex was associated with APOE‐ε4 carriership, a genetic risk factor for AD. EC differences were correlated with age, CSF amyloid levels, and scores on the trail‐making and 15‐object recognition tests.ConclusionOur findings suggest that the APOE‐ε4 genotype affects brain connectivity in regions previously found to be abnormal in AD as a sign of very early disease‐related pathology. These differences were too subtle in healthy elderly to use EC for single‐subject prediction of APOE genotype.

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Section: Discussionmentioning

confidence: 99%

Functional brain network centrality is related to APOE genotype in cognitively normal elderly

et al. 2018

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“…These CSF biomarkers are also prognosis markers since a recent prospective study conduct on 150 AD patients for 5 years revealed that extreme CSF biomarkers levels (high Ttau and P-tau 181 and low A 42 ) are associated with more aggressive diseases leading to an earlier death (Wallin, Blennow et al 2010). Recently, a clinical study of the Alzheimer Disease Neuroimaging Initiative Project has detected an Alzheimer disease signature in the CSF levels of, Aß 42 T-tau and P-tau181 in more than one third of cognitively normal subjects (De Meyer, Shapiro et al 2010). This finding suggests that this CSF signature is present and detectable early during the neurodegenerative process.…”

Section: Which Csf Biochemical Markers Might Allow Us To Detect Alzhementioning

confidence: 99%

Alzheimer’s Diseases: Towards Biomarkers for an Early Diagnosis

Elmoualij¹,

Dupiereux-Fettweis²,

Seguin³

et al. 2011

The Clinical Spectrum of Alzheimer's Disease -the Charge Toward Comprehensive Diagnostic and Therapeutic Strategies

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“…Neuroimaging and CSF parameters increasingly came into use especially in the first decade of the new millennium leading to newly proposed research criteria finally being accepted as a validated instrument to support the diagnostic concept (de Meyer et al, 2010;Dubois et al, 2010;Dubois et al, 2007;Gauthier et al, 2008). Alois Alzheimer first described the hallmarks of AD with plaques and neurofibrillary tangles (NFT) more than a hundred years ago.…”

Section: Definition and Epidemiology Of Rapidly Progressive Admentioning

confidence: 99%

Risk Factors for Disease Progression in Alzheimer's Disease

Schmidt¹,

Wolff²,

Shalash³

et al. 2011

The Clinical Spectrum of Alzheimer's Disease -the Charge Toward Comprehensive Diagnostic and Therapeutic Strategies

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Diagnosis-Independent Alzheimer Disease Biomarker Signature in Cognitively Normal Elderly People

Abstract: To identify biomarker patterns typical for Alzheimer disease (AD) in an independent, unsupervised way, without using information on the clinical diagnosis.

Cited by 398 publications

References 25 publications

Functional brain network centrality is related to APOE genotype in cognitively normal elderly

Functional brain network centrality is related to APOE genotype in cognitively normal elderly

Alzheimer’s Diseases: Towards Biomarkers for an Early Diagnosis

Risk Factors for Disease Progression in Alzheimer's Disease

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