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Temporal association patterns and dynamics of amyloid-β and tau in Alzheimer’s disease. / Alzheimer’s Disease Neuroimaging Initiative.

In: European journal of epidemiology, Vol. 33, No. 7, 2018, p. 657-666.

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Harvard

Alzheimer’s Disease Neuroimaging Initiative 2018, 'Temporal association patterns and dynamics of amyloid-β and tau in Alzheimer’s disease' European journal of epidemiology, vol. 33, no. 7, pp. 657-666. https://doi.org/10.1007/s10654-017-0326-z

APA

Alzheimer’s Disease Neuroimaging Initiative (2018). Temporal association patterns and dynamics of amyloid-β and tau in Alzheimer’s disease. European journal of epidemiology, 33(7), 657-666. https://doi.org/10.1007/s10654-017-0326-z

Vancouver

Alzheimer’s Disease Neuroimaging Initiative. Temporal association patterns and dynamics of amyloid-β and tau in Alzheimer’s disease. European journal of epidemiology. 2018;33(7):657-666. https://doi.org/10.1007/s10654-017-0326-z

Author

Alzheimer’s Disease Neuroimaging Initiative. / Temporal association patterns and dynamics of amyloid-β and tau in Alzheimer’s disease. In: European journal of epidemiology. 2018 ; Vol. 33, No. 7. pp. 657-666.

BibTeX

@article{d7055d0fd11046f5b12735f37b351cee,
title = "Temporal association patterns and dynamics of amyloid-β and tau in Alzheimer’s disease",
abstract = "The elusive relationship between underlying pathology and clinical disease hampers diagnosis of Alzheimer’s disease (AD) and preventative intervention development. We seek to understand the relationship between two classical AD biomarkers, amyloid-β1−42 (Aβ1−42) and total-tau (t-tau), and define their trajectories across disease development, as defined by disease onset at diagnosis of mild cognitive impairment (MCI). Using longitudinal data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), we performed a correlation analysis of biomarkers CSF Aβ1−42 and t-tau, and longitudinal quantile analysis. Using a mixed effects model, with MCI onset as an anchor, we develop linear trajectories to describe the rate of change across disease development. These trajectories were extended through the incorporation of data from cognitively normal, healthy adults (aged 20–62 years) from the literature, to fit sigmoid curves by means of non-linear least squares estimators, to create curves encompassing the 50 years prior to MCI onset. A strong right-angled relationship between the biomarkers Aβ1-42 and t-tau is detected, implying a highly non-linear relationship. The rate of change of Aβ1-42 is correlated with the baseline concentration per quantile, reflecting a reduction in the rate of loss across disease within subjects. Regression models reveal significant amyloid loss relative to MCI onset (− 2.35 pg/mL/year), compared to minimal loss relative to AD onset (− 0.97 pg/mL/year). Tau accumulates consistently relative to MCI and AD onset, (2.05 pg/mL/year) and (2.46 pg/mL/year), respectively. The fitted amyloid curve shows peak loss of amyloid 8.06 years prior to MCI diagnosis, while t-tau exhibits peak accumulation 14.17 years following MCI diagnosis, with the upper limit not yet reached 30 years post diagnosis. Biomarker trajectories aid unbiased, objective assessment of disease progression. Quantitative trajectories are likely to be of use in clinical trial design, as they allow for a more detailed insight into the effectiveness of treatments designed to delay development of biological disease.",
author = "{Alzheimer’s Disease Neuroimaging Initiative} and Ower, {Alison K.} and Christoforos Hadjichrysanthou and Luuk Gras and Jaap Goudsmit and Anderson, {Roy M.} and {de Wolf}, Frank",
year = "2018",
doi = "10.1007/s10654-017-0326-z",
language = "English",
volume = "33",
pages = "657--666",
journal = "European journal of epidemiology",
issn = "0393-2990",
publisher = "Springer Netherlands",
number = "7",

}

RIS

TY - JOUR

T1 - Temporal association patterns and dynamics of amyloid-β and tau in Alzheimer’s disease

AU - Alzheimer’s Disease Neuroimaging Initiative

AU - Ower, Alison K.

AU - Hadjichrysanthou, Christoforos

AU - Gras, Luuk

AU - Goudsmit, Jaap

AU - Anderson, Roy M.

AU - de Wolf, Frank

PY - 2018

Y1 - 2018

N2 - The elusive relationship between underlying pathology and clinical disease hampers diagnosis of Alzheimer’s disease (AD) and preventative intervention development. We seek to understand the relationship between two classical AD biomarkers, amyloid-β1−42 (Aβ1−42) and total-tau (t-tau), and define their trajectories across disease development, as defined by disease onset at diagnosis of mild cognitive impairment (MCI). Using longitudinal data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), we performed a correlation analysis of biomarkers CSF Aβ1−42 and t-tau, and longitudinal quantile analysis. Using a mixed effects model, with MCI onset as an anchor, we develop linear trajectories to describe the rate of change across disease development. These trajectories were extended through the incorporation of data from cognitively normal, healthy adults (aged 20–62 years) from the literature, to fit sigmoid curves by means of non-linear least squares estimators, to create curves encompassing the 50 years prior to MCI onset. A strong right-angled relationship between the biomarkers Aβ1-42 and t-tau is detected, implying a highly non-linear relationship. The rate of change of Aβ1-42 is correlated with the baseline concentration per quantile, reflecting a reduction in the rate of loss across disease within subjects. Regression models reveal significant amyloid loss relative to MCI onset (− 2.35 pg/mL/year), compared to minimal loss relative to AD onset (− 0.97 pg/mL/year). Tau accumulates consistently relative to MCI and AD onset, (2.05 pg/mL/year) and (2.46 pg/mL/year), respectively. The fitted amyloid curve shows peak loss of amyloid 8.06 years prior to MCI diagnosis, while t-tau exhibits peak accumulation 14.17 years following MCI diagnosis, with the upper limit not yet reached 30 years post diagnosis. Biomarker trajectories aid unbiased, objective assessment of disease progression. Quantitative trajectories are likely to be of use in clinical trial design, as they allow for a more detailed insight into the effectiveness of treatments designed to delay development of biological disease.

AB - The elusive relationship between underlying pathology and clinical disease hampers diagnosis of Alzheimer’s disease (AD) and preventative intervention development. We seek to understand the relationship between two classical AD biomarkers, amyloid-β1−42 (Aβ1−42) and total-tau (t-tau), and define their trajectories across disease development, as defined by disease onset at diagnosis of mild cognitive impairment (MCI). Using longitudinal data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), we performed a correlation analysis of biomarkers CSF Aβ1−42 and t-tau, and longitudinal quantile analysis. Using a mixed effects model, with MCI onset as an anchor, we develop linear trajectories to describe the rate of change across disease development. These trajectories were extended through the incorporation of data from cognitively normal, healthy adults (aged 20–62 years) from the literature, to fit sigmoid curves by means of non-linear least squares estimators, to create curves encompassing the 50 years prior to MCI onset. A strong right-angled relationship between the biomarkers Aβ1-42 and t-tau is detected, implying a highly non-linear relationship. The rate of change of Aβ1-42 is correlated with the baseline concentration per quantile, reflecting a reduction in the rate of loss across disease within subjects. Regression models reveal significant amyloid loss relative to MCI onset (− 2.35 pg/mL/year), compared to minimal loss relative to AD onset (− 0.97 pg/mL/year). Tau accumulates consistently relative to MCI and AD onset, (2.05 pg/mL/year) and (2.46 pg/mL/year), respectively. The fitted amyloid curve shows peak loss of amyloid 8.06 years prior to MCI diagnosis, while t-tau exhibits peak accumulation 14.17 years following MCI diagnosis, with the upper limit not yet reached 30 years post diagnosis. Biomarker trajectories aid unbiased, objective assessment of disease progression. Quantitative trajectories are likely to be of use in clinical trial design, as they allow for a more detailed insight into the effectiveness of treatments designed to delay development of biological disease.

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85032202758&origin=inward

UR - https://www.ncbi.nlm.nih.gov/pubmed/29071500

U2 - 10.1007/s10654-017-0326-z

DO - 10.1007/s10654-017-0326-z

M3 - Article

VL - 33

SP - 657

EP - 666

JO - European journal of epidemiology

JF - European journal of epidemiology

SN - 0393-2990

IS - 7

ER -

ID: 5481729