Imperial College London
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Dr Chris Hadjichrysanthou

Faculty of Medicine, School of Public Health

Visiting Researcher
 
 
 
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Contact

 

c.hadjichrysanthou Website

 
 
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Location

 

LG36Medical SchoolSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Ower:2018:10.1007/s10654-017-0326-z,
author = {Ower, AK and Hadjichrysanthou, C and Gras, L and Goudsmit, J and Anderson, RM and de, Wolf F and Alzheimers, Disease Neuroimaging Initiative},
doi = {10.1007/s10654-017-0326-z},
journal = {European Journal of Epidemiology},
pages = {657--666},
title = {Temporal association patterns and dynamics of amyloid-β and tau in Alzheimer's disease},
url = {http://dx.doi.org/10.1007/s10654-017-0326-z},
volume = {33},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
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. Q
AU  - Ower,AK
AU  - Hadjichrysanthou,C
AU  - Gras,L
AU  - Goudsmit,J
AU  - Anderson,RM
AU  - de,Wolf F
AU  - Alzheimers,Disease Neuroimaging Initiative
DO  - 10.1007/s10654-017-0326-z
EP  - 666
PY  - 2018///
SN  - 0393-2990
SP  - 657
TI  - Temporal association patterns and dynamics of amyloid-β and tau in Alzheimer's disease
T2  - European Journal of Epidemiology
UR  - http://dx.doi.org/10.1007/s10654-017-0326-z
UR  - http://hdl.handle.net/10044/1/54086
VL  - 33
ER  -
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