| Title: |
APOE e4 exacerbates age-dependent deficits in cortical microstructure |
| Authors: |
Mak, Foo; Dounavi, Maria-Eleni; Operto, Grégory; Elina, Ziukelis; P Simon, Jones; Low, Audrey; Swann, Peter; Newton, Coco; Terrera, Graciela; Malhotra, Paresh; Koychev, Ivan; Falcon, Carles; Mackay, Clare; Lawlor, Brian; Naci, Lorina; Wells, Katie; Ritchie, Craig; Ritchie, Karen; Su, Li; Gispert, Juan Domingo; O'Brien, John |
| Publisher Information: |
//doi.org/10.1093/braincomms/fcad351; Brain Communications; Oxford University Press |
| Publication Year: |
2024 |
| Collection: |
Apollo - University of Cambridge Repository |
| Subject Terms: |
NODDI; cognitive impairment; neurodegeneration; preclinical dementia |
| Description: |
Acknowledgements: We would like to thank our participant volunteers for taking part in this study. We are also appreciative of the computational infrastructure that enabled data analysis and storage; this was made possible by the High Performance Hubs for Clinical Informatics (HPHI), which was sponsored by the MRC Research Infrastructure Award (MR/M009041/1). ; Funder: Cambridge National Institute for Health and Care Research ; Funder: Biomedical Research Center, and ; Funder: Cambridge National Institute for Health and Care Research, Biomedical Research Center ; The apolipoprotein E ε4 allele is the primary genetic risk factor for the sporadic type of Alzheimer’s disease. However, the mechanisms by which apolipoprotein E ε4 are associated with neurodegeneration are still poorly understood. We applied the Neurite Orientation Dispersion Model to characterise the effects of apolipoprotein ε4 and its interactions with age and education on cortical microstructure in cognitively normal individuals. Data from 1954 participants were included from the PREVENT-Dementia and ALFA (ALzheimer and FAmilies) studies (mean age = 57, 1197 non-carriers, 757 apolipoprotein E ε4 carriers). Structural MRI datasets were processed with FreeSurfer v7.2. The Microstructure Diffusion Toolbox was used to derive Orientation Dispersion Index maps from diffusion MRI datasets. Primary analyses were focused on the (a) main effects of apolipoprotein E ε4, and the (b) interactions of apolipoprotein E ε4 with age and education on lobar and vertex-wise Orientation Dispersion Index and implemented using Permutation Analysis of Linear Models. There were apolipoprotein E ε4 × age interactions in the temporo-parietal and frontal lobes, indicating steeper age-dependent Orientation Dispersion Index changes in apolipoprotein E ε4 carriers. Steeper age-related Orientation Dispersion Index declines were observed among apolipoprotein E ε4 carriers with lower years of education. We demonstrated that apolipoprotein E ε4 worsened age-related Orientation ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/zip; text/xml; application/pdf |
| Language: |
English |
| Relation: |
https://www.repository.cam.ac.uk/handle/1810/364911 |
| Availability: |
https://www.repository.cam.ac.uk/handle/1810/364911 |
| Rights: |
Attribution 4.0 International ; https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.BAD6E1C6 |
| Database: |
BASE |