Fluid Biomarkers in Alzheimer Disease

Blennow, Kaj; Zetterberg, Henrik; Fagan, Anne M.

doi:10.1101/cshperspect.a006221

Cited by 176 publications

(159 citation statements)

References 169 publications

(191 reference statements)

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“…They may be employed for the in vitro monitoring of drug discovery plans intended to identify new molecules inhibiting amyloidogenic mechanisms and to provide surrogate measures assessing treatment efficacy of novel Ab-targeting drugs, which would decrease the time and cut the costs of clinical trials [94]. In addition, biomarkers may help demonstrate the usefulness of a certain therapy in a specific patient, thus assisting the physician to find the proper medication.…”

Section: Discussionmentioning

confidence: 99%

“…As emphasized by Blennow et al (2012) [94], given that the diagnostic accuracy for the combination of CSF Ab 1-42 , t-tau, and p-tau has been reported to be higher than for any biomarker alone [76,93,95,96], a multiparameter assay, utilizing the Luminex TM xMAP technology (Luminex Corporation, Austin, TX, USA) to enable simultaneous quantification of these CSF biomarkers, has been developed [97]. The employment of this assay in multicenter studies on CSF biomarkers has yielded a good diagnostic performance [75,76,79,98].…”

Section: Progression From MCI To Admentioning

confidence: 99%

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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

105

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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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Section: Discussionmentioning

confidence: 99%

Section: Progression From MCI To Admentioning

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

105

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“…One reason is that Tau is elevated in the cerebrospinal fluid (CSF) at an early stage of AD and therefore serves as a biomarker (Hampel et al 2010;Blennow et al 2011). The origin of CSF-Tau is not clear, but dying and disintegrating neurons could contribute to it.…”

Section: Tau Protein In Neurofibrillary Degenerationmentioning

confidence: 99%

Biochemistry and Cell Biology of Tau Protein in Neurofibrillary Degeneration

Mandelkow

2012

Cold Spring Harbor Perspectives in Medicine

705

636

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Tau represents the subunit protein of one of the major hallmarks of Alzheimer disease (AD), the neurofibrillary tangles, and is therefore of major interest as an indicator of disease mechanisms. Many of the unusual properties of Tau can be explained by its nature as a natively unfolded protein. Examples are the large number of structural conformations and biochemical modifications ( phosphorylation, proteolysis, glycosylation, and others), the multitude of interaction partners (mainly microtubules, but also other cytoskeletal proteins, kinases, and phosphatases, motor proteins, chaperones, and membrane proteins). The pathological aggregation of Tau is counterintuitive, given its high solubility, but can be rationalized by short hydrophobic motifs forming b structures. The aggregation of Tau is toxic in cell and animal models, but can be reversed by suppressing expression or by aggregation inhibitors. This review summarizes some of the structural, biochemical, and cell biological properties of Tau and Tau fibers. Further aspects of Tau as a diagnostic marker and therapeutic target, its involvement in other Tau-based diseases, and its histopathology are covered by other chapters in this volume.

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“…Despite substantial progress has been made in the area of biomarker development to confirm the diagnosis at early-clinical AD stages, less is known about the potential role of biomarkers in peripheral tissues in the prediction of AD [58]. Since it has been demonstrated for decades the existence of biochemical changes in the brain preceding the clinical AD onset (up to 20 years in advance) [59,60] it is suggested that these changes may be also indirectly reflected in biological fluids.…”

Section: Biomarkers In Peripheral Tissuesmentioning

confidence: 99%