Effect of <i>APOE ε</i>4 genotype on amyloid‐β, glucose metabolism, and gray matter volume in cognitively normal individuals and amnestic mild cognitive impairment

Li, Weihua; Li, Runtian; Yan, Shaozhen; Zhao, Zirun; Shan, Yi; Qi, Zhigang; Lu, Jie

doi:10.1111/ene.15656

Cited by 3 publications

(1 citation statement)

References 47 publications

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“…Additional longitudinal follow-up studies are therefore warranted. These studies should also analyse the negative modulatory function of the apolipoprotein ε4 genotype, a key risk parameter of AD onset and development (34). Many of our patients also had a positive in ammatory status, which may possibly contribute to increased arterial stiffness (35)(36)(37).…”

Section: Discussionmentioning

confidence: 90%

Early carotid pulse waves are associated with an acceleration of 18 F-FDG PET hypometabolism in Alzheimer’s brain areas

Zimmermann

Joly

Schoepfer

et al. 2023

Preprint

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Background Arterial stiffening likely plays a role in Alzheimer disease (AD) pathogenesis and may also favour a potentially deleterious early return of reflected arterial pressure waves. The current study investigated whether inter-individual variations in arterial stiffness and pressure wave parameters were associated with 18F-FDG positron emission tomography (PET) metabolism in AD-associated brain areas independently of age and before the onset of any neuropsychological disorders.Methods A prospective, large age-range population of 67 patients (17 young, 16 middle-aged, and 34 older adults; 37 women) with normal neuropsychological tests, underwent a: 1) brain 18F-FDG PET, 2) blood pressure recording and 3) carotid/femoral pulse wave-based measurements, including the time-to-peak of the reflected backward carotid pulse wave (bT), on the same day. Multivariate and quantitative voxel-to-voxel analyses (p-voxel < 0.005, corrected for cluster volumes) were conducted to assess associations between vascular parameters and 18F-FDG PET metabolism in AD-associated brain areas.Results In the multivariate analysis, only increased age and decreased bT were independently associated with the decline of metabolic activity in AD-associated brain areas (p < 0.001). In the voxel-to-voxel analysis with age as a covariate, bT was strongly associated with the metabolic activity of 40 clusters in AD-associated brain areas (clusters cumulative volume: 63 cm3; T score max: 5.7).Conclusion In patients, who are still unaffected by neuropsychological disorders, an early reflected arterial pressure wave, as evidenced by a decreased bT value, is strongly associated with an acceleration of the age-related decline in the metabolic activity of AD-associated brain areas.Trial registration : This research study was approved by the local ethics committee (CPP accreditation N°2018/26; date of registration : May,11th 2018).

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Section: Discussionmentioning

confidence: 90%

Early carotid pulse waves are associated with an acceleration of 18 F-FDG PET hypometabolism in Alzheimer’s brain areas

Zimmermann

Joly

Schoepfer

et al. 2023

Preprint

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NOX-induced oxidative stress is a primary trigger of major neurodegenerative disorders

Zilberter,

Tabuena,

Zilberter

2023

Progress in Neurobiology

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Effect of APOE ε4 genotype on amyloid‐β, glucose metabolism, and gray matter volume in cognitively normal individuals and amnestic mild cognitive impairment

Li²,

Yan

et al. 2022

Euro J of Neurology

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Background and purpose The presence of apolipoprotein E ε4 (APOE ε4) is associated with an increased risk of developing Alzheimer disease (AD). The aim of this study was to assess the effects of APOE ε4 on amyloid‐β (Aβ) pathology, glucose metabolism, and gray matter (GM) volume and their longitudinal changes in healthy control (HC) and amnestic mild cognitive impairment (aMCI). Methods We included 50 HCs and 109 aMCI patients from the Alzheimer's Disease Neuroimaging Initiative phase 2/GO based on availability of baseline T1‐weighted magnetic resonance imaging, 18F‐florbetapir positron emission tomography (PET), and 18F‐fluorodeoxyglucose (FDG) PET. Of these, 35 HCs and 67 aMCI patients who underwent 24‐month scans were included for follow‐up study. Results Voxelwise analysis revealed that APOE ε4 carriers exhibited greater baseline Aβ deposition than APOE ε4 noncarriers in both diagnostic groups. However, there was no significant difference between APOE ε4 noncarriers and APOE ε4 carriers in terms of 18F‐FDG PET standardized uptake value ratio and GM volume. Region of interest‐based analysis showed statistically significant greater Aβ deposition in APOE ε4 carriers than APOE ε4 noncarriers only in aMCI patients. Furthermore, APOE ε4 carriers generally exhibited a greater magnitude and spatial extent of longitudinal changes in Aβ deposition than APOE ε4 noncarriers in both diagnostic groups. Conclusions Our findings suggest a differential effect of APOE ε4 on Aβ pathology, glucose metabolism, and GM volume. Studying APOE ε4‐related brain changes with neuroimaging biomarkers in preclinical AD offers an opportunity to further our understanding of the pathophysiology of AD at an early stage.

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Effect of APOE ε4 genotype on amyloid‐β, glucose metabolism, and gray matter volume in cognitively normal individuals and amnestic mild cognitive impairment

Cited by 3 publications

References 47 publications

Early carotid pulse waves are associated with an acceleration of 18 F-FDG PET hypometabolism in Alzheimer’s brain areas

Early carotid pulse waves are associated with an acceleration of 18 F-FDG PET hypometabolism in Alzheimer’s brain areas

NOX-induced oxidative stress is a primary trigger of major neurodegenerative disorders

Effect of APOE ε4 genotype on amyloid‐β, glucose metabolism, and gray matter volume in cognitively normal individuals and amnestic mild cognitive impairment

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