Salami, A;
Adolfsson, R;
Andersson, M;
Blennow, K;
Lundquist, A;
Adolfsson, AN;
Schöll, M;
... Nyberg, L; + view all
(2021)
Association of APOE ɛ4 and Plasma p-tau181 with Preclinical Alzheimer's Disease and Longitudinal Change in Hippocampus Function.
Journal of Alzheimer's Disease
10.3233/JAD-210673.
(In press).
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Abstract
BACKGROUND: The Apolipoprotein E (APOE) ɛ4 allele has been linked to increased tau phosphorylation and tangle formation. APOE ɛ4 carriers with elevated tau might be at the higher risk for AD progression. Previous studies showed that tau pathology begins early in areas of the medial temporal lobe. Similarly, APOE ɛ4 carriers showed altered hippocampal functional integrity. However, it remains unknown whether elevated tau accumulation on hippocampal functional changes would be more pronounced for APOE ɛ4 carriers. OBJECTIVE: We related ɛ4 carriage to levels of plasma phosphorylated tau (p-tau181) up to 15 years prior to AD onset. Furthermore, elevated p-tau181 was explored in relation to longitudinal changes in hippocampal function and connectivity. METHODS: Longitudinal population-based study. Plasma p-tau181 was analyzed in 142 clinically defined Alzheimer's disease (AD) cases and 126 controls. The longitudinal analysis involved 87 non-demented individuals with two waves of plasma samples and three waves of functional magnetic resonance imaging during rest and memory encoding. RESULTS: Increased p-tau181 was observed for both ɛ4 carriers and non-carriers close to AD, but exclusively for ɛ4 carriers in the early preclinical groups (7- and 13-years pre-AD). In ɛ4 carriers, longitudinal p-tau181 increase was paralleled by elevated local hippocampal connectivity at rest and subsequent reduction of hippocampus encoding-related activity. CONCLUSION: Our findings support an association of APOE ɛ4 and p-tau181 with preclinical AD and hippocampus functioning.
| Type: | Article |
|---|---|
| Title: | Association of APOE ɛ4 and Plasma p-tau181 with Preclinical Alzheimer's Disease and Longitudinal Change in Hippocampus Function |
| Location: | Netherlands |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3233/JAD-210673 |
| Publisher version: | http://doi.org/10.3233/JAD-210673 |
| Language: | English |
| Additional information: | © 2021 – The authors. Published by IOS Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (CC BY-NC 4.0) |
| Keywords: | APOE, Alzheimer’s disease, fMRI, hippocampus, longitudinal, magnetic resonance imaging, p-tau181, phosphorylated tau, population-based |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10141374 |
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