Plasma multianalyte profiling in mild cognitive impairment and Alzheimer disease

Hu, William T.; Holtzman, David M.; Fagan, Anne M.; Shaw, Leslie M.; Perrin, Richard J.; Arnold, Steven E.; Grossman, Murray; Xiong, Chengjie; Craig‐Schapiro, Rebecca; Clark, Christopher M.; Pickering, Eve H.; Kühn, Max; Chen, Y.; Deerlin, Vivianna M. Van; McCluskey, Leo; Elman, Lauren; Karlawish, Jason; Chen‐Plotkin, Alice S.; Hurtig, Howard I.; Siderowf, Andrew; Swenson, Frank; Lee, V. M.- Y.; Morris, John C.; Trojanowski, John Q.; Soares, Holly

doi:10.1212/wnl.0b013e318266fa70

Cited by 210 publications

(184 citation statements)

References 42 publications

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“…SAP has been previously reported as a diagnostic AD candidate biomarker in the literature [4] albeit it with conflicting direction of association [3,10,30,31]. Although we found changes in SAP to be associated with rate of decline we did not observe significant changes of SAP when comparing diagnostic groups against controls.…”

Section: Discussioncontrasting

confidence: 84%

Longitudinal Protein Changes in Blood Plasma Associated with the Rate of Cognitive Decline in Alzheimer’s Disease

Sattlecker

Khondoker

Proitsi

et al. 2016

JAD

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Biomarkers of Alzheimer's disease (AD) progression are needed to support the development of urgently needed disease modifying drugs. We employed a SOMAscan assay for quantifying 1,001 proteins in blood samples from 90 AD subjects, 37 stable mild cognitive impaired (MCI) subjects, 39 MCI subjects converting to AD within a year and 69 controls at baseline and one year follow up. We used linear mixed effects models to identify proteins changing significantly over one year with the rate of cognitive decline, which was quantified as the reduction of Mini Mental State Examination (MMSE) scores. Additionally we investigated proteins changing differently across disease groups and during the conversion from MCI to AD. We found that levels of proteins belonging to the complement cascade increase significantly in fast declining AD patients. Longitudinal changes in the complement cascade might be a surrogate biomarker for disease progression. Additionally we found that members of the cytokine-cytokine receptor interaction pathway change during AD when compared to healthy aging subjects.

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Section: Discussioncontrasting

confidence: 84%

Longitudinal Protein Changes in Blood Plasma Associated with the Rate of Cognitive Decline in Alzheimer’s Disease

Sattlecker

Khondoker

Proitsi

et al. 2016

JAD

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“…Mass spectrometry-based methods, together with innovative tools in progress, are welcomed because they will significantly improve the ability to detect blood markers [127,128]. By simultaneously quantifying the levels of many plasma analytes, biomarker patterns successfully distinguishing AD patients from controls [129] or associated with MCI or AD have been disclosed [130]. Since the activities of most molecules are connected to immune regulation and inflammatory pathways, the existence of an inflammatory process in AD has been firmly proposed [131,132].…”

Section: Blood Prospective Candidate Biomarkersmentioning

confidence: 99%

“…However, two analyses, utilizing large and well-characterized clinical cohorts, have discovered that a set of inflammatory molecules display modified expression as a function of AD [130,134]. Moreover, both Doecke et al (2012) [134] and O'Bryant et al (2011) [135] have found diagnostic accuracy across cohorts employing biomarker algorithms/profiles.…”

Section: Blood Prospective Candidate Biomarkersmentioning

confidence: 99%

Perspective on future role of biological markers in clinical therapy trials of Alzheimer's disease: A long-range point of view beyond 2020

Hampel

Lista

Teipel

et al. 2014

Biochemical Pharmacology

102

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Recent advances in understanding the molecular mechanisms underlying various paths toward the pathogenesis of Alzheimer's disease (AD) has begun to provide new insight for interventions to modify disease progression. The evolving knowledge gained from multidisciplinary basic research has begun to identify new concepts for treatments and distinct classes of therapeutic targets; as well as putative disease-modifying compounds that are now being tested in clinical trials. There is a mounting consensus that such disease modifying compounds and/or interventions are more likely to be effectively administered as early as possible in the cascade of pathogenic processes preceding and underlying the clinical expression of AD. The budding sentiment is that "treatments" need to be applied before various molecular mechanisms converge into an irreversible pathway leading to morphological, metabolic and functional alterations that characterize the pathophysiology of AD. In light of this, biological indicators of pathophysiological mechanisms are desired to chart and detect AD throughout the asymptomatic early molecular stages into the prodromal and early dementia phase. A major conceptual development in the clinical AD research field was the recent proposal of new diagnostic criteria, which specifically incorporate the use of biomarkers as defining criteria for preclinical stages of AD. This paradigm shift in AD definition, conceptualization, operationalization, detection and diagnosis represents novel fundamental opportunities for the modification of interventional trial designs. This perspective summarizes not only present knowledge regarding biological markers but also unresolved questions on the status of surrogate indicators for detection of the disease in asymptomatic people and diagnosis of AD

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“…In addition, regression analysis showed CSF Ab42 levels and t-tau/Ab42 ratios to correlate with the number of APOE4 alleles and plasma levels of B-type natriuretic peptide and pancreatic polypeptide [75]. Consistent with putative biomarkers identified in CSF, the ratio of plasma Aß1-42/1-40 has also been proposed as a more accurate indicator than each peptide on its own.…”

Section: Resultsmentioning

confidence: 66%

P1–234: Circulating miRNA biomarkers for Alzheimer's disease

Kumar

Dezső

MacKenzie

et al. 2013

Alzheimer's & Dementia

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A minimally invasive diagnostic assay for early detection of Alzheimer's disease (AD) is required to select optimal patient groups in clinical trials, monitor disease progression and response to treatment, and to better plan patient clinical care. Blood is an attractive source for biomarkers due to minimal discomfort to the patient, encouraging greater compliance in clinical trials and frequent testing. MiRNAs belong to the class of non-coding regulatory RNA molecules of ,22 nt length and are now recognized to regulate ,60% of all known genes through post-transcriptional gene silencing (RNAi). They have potential as useful biomarkers for clinical use because of their stability and ease of detection in many tissues, especially blood. Circulating profiles of miRNAs have been shown to discriminate different tumor types, indicate staging and progression of the disease and to be useful as prognostic markers. Recently their role in neurodegenerative diseases, both as diagnostic biomarkers as well as explaining basic disease etiology has come into focus. Here we report the discovery and validation of a unique circulating 7-miRNA signature (hsa-let-7d-5p, hsa-let-7g-5p, hsa-miR-15b-5p, hsa-miR-142-3p, hsamiR-191-5p, hsa-miR-301a-3p and hsa-miR-545-3p) in plasma, which could distinguish AD patients from normal controls (NC) with .95% accuracy (AUC of 0.953). There was a .2 fold difference for all signature miRNAs between the AD and NC samples, with p-values,0.05. Pathway analysis, taking into account enriched target mRNAs for these signature miRNAs was also carried out, suggesting that the disturbance of multiple enzymatic pathways including lipid metabolism could play a role in AD etiology.

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Plasma multianalyte profiling in mild cognitive impairment and Alzheimer disease

Cited by 210 publications

References 42 publications

Longitudinal Protein Changes in Blood Plasma Associated with the Rate of Cognitive Decline in Alzheimer’s Disease

Longitudinal Protein Changes in Blood Plasma Associated with the Rate of Cognitive Decline in Alzheimer’s Disease

Perspective on future role of biological markers in clinical therapy trials of Alzheimer's disease: A long-range point of view beyond 2020

P1–234: Circulating miRNA biomarkers for Alzheimer's disease

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