APOE ε4 exacerbates age-dependent deficits in cortical microstructure

被引：5

作者：

Mak, Elijah ^{[1
]}

Dounavi, Maria-Eleni ^{[1
]}

Operto, Gregory ^{[2
]}

Ziukelis, Elina T. ^{[1
]}

Jones, Peter Simon ^{[3
]}

Low, Audrey ^{[1
]}

Swann, Peter ^{[1
]}

Newton, Coco ^{[1
]}

Muniz Terrera, Graciela ^{[4
]}

Malhotra, Paresh ^{[5
]}

Koychev, Ivan ^{[6
]}

Falcon, Carles ^{[2
,7
,8
]}

Mackay, Clare ^{[6
]}

Lawlor, Brian ^{[9
]}

Naci, Lorina ^{[9
]}

Wells, Katie ^{[4
]}

Ritchie, Craig ^{[4
]}

Ritchie, Karen ^{[10
,11
]}

Su, Li ^{[1
]}

Gispert, Juan Domingo ^{[2
,7
,8
]}

O'Brien, John T. ^{[1
]}

机构：

[1] Univ Cambridge, Sch Clin Med, Dept Psychiat, Level E4 Cambridge Biomed Campus, Cambridge CB2 0QQ, England

[2] Pasqual Maragall Fdn, Barcelonasseta Brain Res Ctr, Barcelona 08005, Spain

[3] Univ Cambridge, Dept Clin Neurosci, Cambridge CB2 0SZ, England

[4] Univ Edinburgh, Ctr Dementia Prevent, Edinburgh EH4 2XU, Scotland

[5] Imperial Coll, Dept Brain Sci, London W12 0NN, England

[6] Univ Oxford, Dept Psychiat, Oxford OX3 7JX, England

[7] IMIM Hosp Mar Med Res Inst, Barcelona 08003, Spain

[8] Ctr Invest Biomed Red Bioingn Biomat & Nanomed CI, Madrid 28029, Spain

[9] Univ Dublin, Inst Neurosci, Trinity Coll Dublin, Dublin D02 PX31, Ireland

[10] Inst Natl St & Rech Med, Neuropsychiat U1061, F-34093 Montpellier, France

[11] Univ Montpellier, Fac Med, F-34093 Montpellier, France

来源：

BRAIN COMMUNICATIONS | 2023年 / 6卷 / 01期

关键词：

NODDI; neurodegeneration; cognitive impairment; preclinical dementia; NEURITE ORIENTATION DISPERSION; HUMAN CEREBRAL-CORTEX; ALZHEIMERS-DISEASE; APOLIPOPROTEIN-E; GRAY-MATTER; DENDRITIC COMPLEXITY; HIPPOCAMPAL SUBFIELDS; HYPOTHETICAL MODEL; MOUSE MODEL; DENSITY;

D O I：

10.1093/braincomms/fcad351

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

The apolipoprotein E e4 allele is the primary genetic risk factor for the sporadic type of Alzheimer's disease. However, the mechanisms by which apolipoprotein E e4 are associated with neurodegeneration are still poorly understood. We applied the Neurite Orientation Dispersion Model to characterize the effects of apolipoprotein e4 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 and 757 apolipoprotein E e4 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 (i) the main effects of apolipoprotein E e4, and (ii) the interactions of apolipoprotein E e4 with age and education on lobar and vertex-wise Orientation Dispersion Index and implemented using Permutation Analysis of Linear Models. There were apolipoprotein E e4 x age interactions in the temporo-parietal and frontal lobes, indicating steeper age-dependent Orientation Dispersion Index changes in apolipoprotein E e4 carriers. Steeper age-related Orientation Dispersion Index declines were observed among apolipoprotein E e4 carriers with lower years of education. We demonstrated that apolipoprotein E e4 worsened age-related Orientation Dispersion Index decreases in brain regions typically associated with atrophy patterns of Alzheimer's disease. This finding also suggests that apolipoprotein E e4 may hasten the onset age of dementia by accelerating age-dependent reductions in cortical Orientation Dispersion Index. Mak et al. demonstrated a significantly more pronounced age-related decline in cortical Orientation Dispersion Index amongst cognitively normal midlife carriers of apolipoprotein E e4 compared with non-carriers. Apolipoprotein E e4 may hasten the onset age of dementia by accelerating age-dependent deficits of cortical microstructure in Alzheimer's disease regions. Additional longitudinal studies are needed to verify this hypothesis. Graphical Abstract

引用

页数：14

共 77 条

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