Injury markers predict time to dementia in subjects with MCI and amyloid pathology

Rossum, Ineke A. van; Vos, Stephanie J.B.; Burns, Leah; Knol, Dirk L.; Scheltens, Philip; Soininen, Hilkka; Wahlund, Lars‐Olof; Hampel, Harald; Tsolaki, Magda; Minthon, Lennart; L’Italien, G.; Flier, Wiesje M. van der; Teunissen, Charlotte E.; Blennow, Kaj; Barkhof, Frederik; Rueckert, Daniel; Wolz, Robin; Verhey, Frans R.J.; Visser, Pieter Jelle

doi:10.1212/wnl.0b013e3182704056

Cited by 133 publications

(87 citation statements)

References 30 publications

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“…Considering the age-dependent tau accumulation found in HC in the present study, tau may have a primary triggering effect. When gradually accumulated tau exceeds a certain threshold, pathological Aβ accumulation may start inducing rapid AD progress (tau first, amyloid second theory) [4,5,14].…”

Section: Discussionmentioning

confidence: 99%

Localized Accumulation of Tau without Amyloid-Beta in Aged Brains Measured with [11C]PBB3 and [11C]Pib Positron Emission Tomography

Kikukawa¹,

Saito²,

Hasegawa³

et al. 2017

J Alzheimers Dis Parkinsonism

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Section: Discussionmentioning

confidence: 99%

Localized Accumulation of Tau without Amyloid-Beta in Aged Brains Measured with [11C]PBB3 and [11C]Pib Positron Emission Tomography

Kikukawa¹,

Saito²,

Hasegawa³

et al. 2017

J Alzheimers Dis Parkinsonism

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“…These data support the hypothesis that modified Ab metabolism precedes tau-related disease and neuronal degeneration. The other study has disclosed that MCI subjects with elevated concentrations of injury markersnamely, t-tau and p-tau -may develop faster, therefore presenting shorter time to conversion [101]. Since both analyses are crosssectional in regards to the biomarker data, the use of multiple longitudinal CSF specimens is necessary to detect the time point at which CSF biomarkers convert from physiologic to pathologic values.…”

Section: Time Course Of Ad 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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“…After an average follow-up of 9 years, approximately 90% of the subjects with a combination of abnormal Ab1-42 and tau in CSF converted to AD-type dementia [4]. We found that 30% of the subjects with abnormal CSF Ab1-42 and normal injury markers converted to AD-type dementia after 4 years compared with 80-90% of the subjects with abnormal CSF Ab1-42 and one or more abnormal injury markers [15].…”

Section: Interpretation Of Ad Biomarker Scoresmentioning

confidence: 63%

Disclosure of Alzheimer’s Disease Biomarker Status in Subjects with Mild Cognitive Impairment

et al. 2012

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Injury markers predict time to dementia in subjects with MCI and amyloid pathology

Abstract: In subjects with MCI and evidence of amyloid pathology, the injury markers CSF t-tau and p-tau and hippocampal atrophy can predict further cognitive decline.

Cited by 133 publications

References 30 publications

Localized Accumulation of Tau without Amyloid-Beta in Aged Brains Measured with [11C]PBB3 and [11C]Pib Positron Emission Tomography

Localized Accumulation of Tau without Amyloid-Beta in Aged Brains Measured with [11C]PBB3 and [11C]Pib Positron Emission Tomography

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

Disclosure of Alzheimer’s Disease Biomarker Status in Subjects with Mild Cognitive Impairment

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