在认知正常的β-淀粉样蛋白积累的男性中，脑血流对神经激活的反应减少。

IF 7.9 1区医学 Q1 CLINICAL NEUROLOGY

Alzheimer's Research & Therapy Pub Date : 2025-01-04 DOI:10.1186/s13195-024-01652-z

Mark Bitsch Vestergaard, Aftab Bakhtiari, Merete Osler, Erik Lykke Mortensen, Ulrich Lindberg, Ian Law, Martin Lauritzen, Krisztina Benedek, Henrik Bo Wiberg Larsson

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ΔCBFVis.Act. was measured using arterial spin labelling (ASL) combined with blood-oxygen-level-dependent (BOLD) MRI. Neuronal activation was obtained by visual stimulation by a flickering checkerboard presented on a screen in the MRI-scanner. Brain Aβ accumulation and cerebral glucose metabolism were assessed by PET imaging using the radiotracers [11C]Pittsburgh Compound-B (PiB) and [18F]Fluorodeoxyglucose (FDG), respectively. Cortical thickness was measured from structural MRI.Results: ΔCBFVis.Act. correlated negatively ( <math><mi>β</mi></math> = -32.1 [95% confidence interval (CI): -60.2; -4.1], r = -0.30, p = 0.025) with PiB standardized uptake value ratio (SUVr) in the brain regions activated by visual stimulation. ΔCBFVis.Act. did not correlate with FDG SUVr ( <math><mi>β</mi></math> = 1.9 [CI: -23.8; 27.6], r = 0.02, p = 0.88) or cortical thickness ( <math><mi>β</mi></math> = 10.3 [CI: -8.4; 29.0], r = 0.15, p = 0.27) in the activated brain regions. 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引用次数: 0

摘要

背景：β-淀粉样蛋白（a β）在大脑中的积累是阿尔茨海默病（AD）的一个标志。大脑中Aβ的沉积会引发恶化的通路，最终导致AD。然而，确切的机制尚不清楚。可能的途径是Aβ影响脑血管，导致脑血管功能不足。在本研究中，我们研究了a β积累是否与视觉刺激下神经元激活的脑血流量反应（CBF）降低有关（ΔCBFVis.Act.），研究对象是来自丹麦大都会男性出生队列的认知正常受试者。方法：64名受试者参与本研究。ΔCBFVis.Act。采用动脉自旋标记（ASL）联合血氧水平依赖（BOLD） MRI测量。神经元的激活是通过在核磁共振扫描仪的屏幕上显示一个闪烁的棋盘的视觉刺激获得的。采用放射性示踪剂[11C]Pittsburgh复合物- b （PiB）和[18F]Fluorodeoxyglucose (FDG)， PET显像评估脑Aβ积累和脑葡萄糖代谢。结构MRI测量皮质厚度。结果:ΔCBFVis.Act。相关负相关(β = -32.1[95%置信区间（CI）： -60.2；-4.1], r = -0.30, p = 0.025)与视觉刺激激活的脑区PiB标准化摄取值比（SUVr）有关。ΔCBFVis.Act。与FDG SUVr无关(β = 1.9 [CI: -23.8；27.6), r = 0.02, p = 0.88)或皮质厚度(β= 10.3 (CI: -8.4;29.0], r = 0.15, p = 0.27)。在视觉刺激激活的区域，静息CBF与PiB SUVr也不相关(β = -17.8 [CI:-71.9；36.2), r = - 0.09, p = 0.51)和剩余皮层(β= 5.2 (CI: -3.9;[14.2], r = 0.15, p = 0.26)。结论：我们发现高PiB SUVr与减少CBF对神经元激活的反应之间存在相关性，表明a β积累与脑血管功能受损之间存在联系。这种损伤与皮质变薄或低代谢无关，这表明影响脑血管功能的a β积累可能是导致神经退行性疾病的早期病理。

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The cerebral blood flow response to neuroactivation is reduced in cognitively normal men with β-amyloid accumulation.

Background: Accumulation of β-amyloid (Aβ) in the brain is a hallmark of Alzheimer's Disease (AD). Cerebral deposition of Aβ initiates deteriorating pathways which eventually can lead to AD. However, the exact mechanisms are not known. A possible pathway could be that Aβ affects the cerebral vessels, causing inadequate cerebrovascular function. In the present study, we examined if Aβ accumulation is associated with a reduced cerebral blood flow response (CBF) to neuronal activation by visual stimulation (ΔCBF_Vis.Act.) in cognitively normal subjects from the Metropolit Danish Male Birth Cohort.

Methods: 64 subjects participated in the present study. ΔCBF_Vis.Act. was measured using arterial spin labelling (ASL) combined with blood-oxygen-level-dependent (BOLD) MRI. Neuronal activation was obtained by visual stimulation by a flickering checkerboard presented on a screen in the MRI-scanner. Brain Aβ accumulation and cerebral glucose metabolism were assessed by PET imaging using the radiotracers [¹¹C]Pittsburgh Compound-B (PiB) and [¹⁸F]Fluorodeoxyglucose (FDG), respectively. Cortical thickness was measured from structural MRI.

Results: ΔCBF_Vis.Act. correlated negatively ( $β$ = -32.1 [95% confidence interval (CI): -60.2; -4.1], r = -0.30, p = 0.025) with PiB standardized uptake value ratio (SUVr) in the brain regions activated by visual stimulation. ΔCBF_Vis.Act. did not correlate with FDG SUVr ( $β$ = 1.9 [CI: -23.8; 27.6], r = 0.02, p = 0.88) or cortical thickness ( $β$ = 10.3 [CI: -8.4; 29.0], r = 0.15, p = 0.27) in the activated brain regions. Resting CBF did not correlate with PiB SUVr neither in the regions activated by visual stimulation ( $β$ = -17.8 [CI:-71.9; 36.2], r =- 0.09, p = 0.51) nor in the remaining cortex ( $β$ = 5.2 [CI:-3.9; 14.2], r = 0.15, p = 0.26).

Conclusion: We found a correlation between high PiB SUVr and reduced CBF response to neuronal activation, indicating a link between Aβ accumulation and impaired cerebrovascular function. The impairment was not associated with cortical thinning or hypometabolism, suggesting that Aβ accumulation affecting brain vessel function could be a very early pathology leading to neurodegenerative disease.

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来源期刊

Alzheimer's Research & Therapy 医学-神经病学

CiteScore

13.10

自引率

3.30%

发文量

172

审稿时长

>12 weeks

期刊介绍： Alzheimer's Research & Therapy is an international peer-reviewed journal that focuses on translational research into Alzheimer's disease and other neurodegenerative diseases. It publishes open-access basic research, clinical trials, drug discovery and development studies, and epidemiologic studies. The journal also includes reviews, viewpoints, commentaries, debates, and reports. All articles published in Alzheimer's Research & Therapy are included in several reputable databases such as CAS, Current contents, DOAJ, Embase, Journal Citation Reports/Science Edition, MEDLINE, PubMed, PubMed Central, Science Citation Index Expanded (Web of Science) and Scopus.