Almanza Dustin Loren V, Koletar Margaret M, Lai Aaron Y, Lam Wilfred W, Joo Lewis, Hill Mary E, Stanisz Greg J, McLaurin JoAnne, Stefanovic Bojana
Physical Sciences Platform, Sunnybrook Research Institute, Toronto, Canada.
Department of Medical Biophysics, University of Toronto, Toronto, Canada.
Theranostics. 2024 Oct 28;14(19):7405-7423. doi: 10.7150/thno.98793. eCollection 2024.
While obesity has been linked to both increased and decreased rate of cognitive decline in Alzheimer's Disease (AD) patients, there is no consensus on the interaction between obesity and AD. The TgF344-AD rat model was used to investigate the effects of high carbohydrate, high fat (HCHF) diet on brain glucose metabolism and hemodynamics in the presence or absence of AD transgenes, in presymptomatic (6-month-old) vs. symptomatic (12-month-old) stages of AD progression using non-invasive neuroimaging. In presymptomatic AD, HCHF exerted detrimental effects, attenuating both hippocampal glucose uptake and resting perfusion in both non-transgenic and TgAD cohorts, when compared to CHOW-fed cohorts. In contrast, HCHF consumption was beneficial in established AD, resolving the AD-progression associated attenuation in hippocampal glucose uptake and functional hyperemia. Whereas HCHF was harmful to the presymptomatic AD brain, it ameliorated deficits in hippocampal metabolism and neurovascular coupling in symptomatic TgAD rats.
虽然肥胖与阿尔茨海默病（AD）患者认知衰退率的增加和降低都有关联，但肥胖与AD之间的相互作用尚无定论。使用TgF344-AD大鼠模型，通过非侵入性神经成像技术，研究在有或没有AD转基因的情况下，高碳水化合物、高脂肪（HCHF）饮食对处于AD进展的症状前（6个月大）与症状期（12个月大）阶段的大脑葡萄糖代谢和血流动力学的影响。在症状前AD阶段，与喂食普通饲料的大鼠组相比，HCHF饮食产生了有害影响，使非转基因和TgAD大鼠组的海马葡萄糖摄取和静息灌注均减弱。相比之下，在已确诊的AD中，食用HCHF饮食有益，可解决与AD进展相关的海马葡萄糖摄取和功能性充血减弱问题。虽然HCHF饮食对症状前AD大脑有害，但它改善了症状性TgAD大鼠海马代谢和神经血管耦合的缺陷。
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