Neurodegenerative disease biomarkers: Guideposts for disease prevention through early diagnosis and intervention

Trojanowski, John Q.; Hampel, Harald

doi:10.1016/j.pneurobio.2011.07.004

Cited by 43 publications

(23 citation statements)

References 31 publications

(64 reference statements)

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“…Following the hypothetical model of dynamic biomarkers for AD pathology, the aggregation and deposition of Aβ 42 is hypothesized to precede clinical symptoms by many years and to occur before biomarker-detectable tau pathology, NFT formation, and neuronal degeneration [3,47,48]. Thus, the drop in CSF Aβ 42 should come before the increase in CSF tau proteins (Fig.…”

Section: Which Csf Biomarkers Are the Most Appropriate?mentioning

confidence: 99%

“…Alzheimer’s disease (AD) is a complex progressive neurodegenerative disease affecting approximately 14 million people in Europe and the United States [1,2], including almost one-half of the population aged >85 years (43%) [2,3]. In the early stages, the pathologic changes in AD primarily affect the medial temporal lobe, subsequently progressing to neocortical-associated areas [4,5].…”

Section: Introductionmentioning

confidence: 99%

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Clinical utility of cerebrospinal fluid biomarkers in the diagnosis of early Alzheimer's disease

Blennow

Dubois

Fagan³

et al. 2014

Alzheimer's & Dementia

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385

304

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Several potential disease-modifying drugs for Alzheimer’s disease (AD) have failed to show any effect on disease progression in clinical trials, conceivably because the AD subjects are already too advanced to derive clinical benefit from treatment and because diagnosis based on clinical criteria alone introduces a high misdiagnosis rate. Thus, well-validated biomarkers for early detection and accurate diagnosis are crucial. Low cerebrospinal fluid (CSF) concentrations of the amyloid-β (Aβ1-42) peptide, in combination with high total tau and phosphorylated tau, are sensitive and specific biomarkers highly predictive of progression to AD dementia in patients with mild cognitive impairment. However, interlaboratory variations in the results seen with currently available immunoassays are of concern. Recent worldwide standardization efforts and quality control programs include standard operating procedures for both preanalytical (e.g., lumbar puncture and sample handling) and analytical (e.g., preparation of calibration curve) procedures. Efforts are also ongoing to develop highly reproducible assays on fully automated instruments. These global standardization and harmonization measures will provide the basis for the generalized international application of CSF bio-markers for both clinical trials and routine clinical diagnosis of AD.

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Section: Which Csf Biomarkers Are the Most Appropriate?mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Clinical utility of cerebrospinal fluid biomarkers in the diagnosis of early Alzheimer's disease

Blennow

Dubois

Fagan³

et al. 2014

Alzheimer's & Dementia

Self Cite

385

304

View full text Add to dashboard Cite

show abstract

“…However, significant indications on the existing state of the biomedicine on candidate markers of AD resulting from multiple analytical platforms -encompassing (I) structural/functional/metabolic neuroimaging modalities, (II) neurochemistry methods based on CSF and blood (plasma/serum) examination, (III) neurogenetic analyses, and (IV) procedures for cognitive and functional assessment -have been supplied [5][6][7][8][9][10][11][12][13].…”

Section: Introductionmentioning

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

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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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“…Even though a definitive diagnosis of AD can only be made by means of brain tissue postmortem assessment, scientific advances have made it possible for early detection of abnormalities, e.g., cognitive decline, memory deficits and behavioral problems (Millard et al 2011;Woods et al 2003;Santacruz and Swagerty 2001). This is made possible by use of biological markers to detect biochemical changes in the cerebrospinal fluid (CSF), presence of filamentous aggregates of misfolded Ab, tau and a-synuclein; and presence of neurotrophins such as cocaine-and amphetamine-regulated transcript (CART) (Forlenza et al 2010;Trojanowski and Hampel 2011;Mao 2012;Galvin and Sadowsky 2012). A current study, however, has pointed out that the assessment of levels of Ab in plasma and CSF may not be entirely specific to AD (Verbeek et al 2009).…”

Section: Diagnosis and Treatment Of Sdmentioning

confidence: 93%

Senile Dementia from Neuroscientific and Islamic Perspectives

et al. 2015

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Diseases involving the nervous system drastically change lives of victims and commonly increase dependency on others. This paper focuses on senile dementia from both the neuroscientific and Islamic perspectives, with special emphasis on the integration of ideas between the two different disciplines. This would enable effective implementation of strategies to address issues involving this disease across different cultures, especially among the world-wide Muslim communities. In addition, certain incongruence ideas on similar issues can be understood better. The former perspective is molded according to conventional modern science, while the latter on the analysis of various texts including the holy Qur'an, sunnah [sayings and actions of the Islamic prophet, Muhammad (pbuh)] and writings of Islamic scholars. Emphasis is particularly given on causes, symptoms, treatments and prevention of dementia.

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Neurodegenerative disease biomarkers: Guideposts for disease prevention through early diagnosis and intervention

Cited by 43 publications

References 31 publications

Clinical utility of cerebrospinal fluid biomarkers in the diagnosis of early Alzheimer's disease

Clinical utility of cerebrospinal fluid biomarkers in the diagnosis of early 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

Senile Dementia from Neuroscientific and Islamic Perspectives

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