Almanza Dustin Loren V, Trevisiol Andrea, Koletar Margaret M, Lai Aaron Y, Ribeiro Jessica A, 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.
Alzheimers Dement. 2025 Oct;21(10):e70708. doi: 10.1002/alz.70708.
Alzheimer's disease (AD) involves progressive hippocampal dysfunction and atrophy. Obesity, common in AD patients, is a known dementia risk factor. Studying their interaction is difficult in humans due to AD's slow progression. Experimental AD models comorbid with obesity are needed for translational insights. This study examined the effects of a high-carbohydrate, high-fat (HCHF) diet in 12-month-old TgF344-AD rats.
Nontransgenic (nTg) and TgAD rats received CHOW or CHOW and HCHF diet items from 9 to 12 months of age. Hippocampal neurovascular function was assessed using pseudo continuous arterial spin labeling (pCASL)-MRI during forepaw stimulation. Neuronal activity was recorded with Neuropixels probes.
CHOW-fed TgAD rats showed reduced hippocampal cerebral blood flow (CBF), CBF changes spread, and neuronal power responses to somatosensory stimulation; all of these deficits were improved on the HCHF diet.
This approach provides a sensitive, task-free assay of hippocampal neurovascular coupling. The transiently improved neurovascular and electrophysiological metrics in HCHF-fed TgAD rats may be a manifestation of metabolically dysregulated AD brain benefitting from increased metabolite availability.
Pseudo-continuous arterial spin labeling (pCASL) magnetic resonance imaging (MRI) -based characterization of hippocampal functional hyperemia. Hippocampal functional hyperemia is attenuated in symptomatic Alzheimer's disease (AD) pathology. A high-carbohydrate, high-fat (HCHF) diet transiently restores hippocampal functional hyperemia in symptomatic AD pathology.
阿尔茨海默病（AD）涉及海马体功能逐渐衰退和萎缩。肥胖在AD患者中很常见，是已知的痴呆风险因素。由于AD进展缓慢，在人类中研究它们之间的相互作用很困难。需要有与肥胖共病的实验性AD模型来获得转化医学方面的见解。本研究考察了高碳水化合物、高脂肪（HCHF）饮食对12月龄TgF344-AD大鼠的影响。
非转基因（nTg）和TgAD大鼠在9至12月龄期间接受普通饲料或普通饲料以及HCHF饮食。在前爪刺激期间，使用伪连续动脉自旋标记（pCASL）-MRI评估海马神经血管功能。用神经像素探针记录神经元活动。
喂食普通饲料的TgAD大鼠海马脑血流量（CBF）降低、CBF变化范围扩大以及对体感刺激的神经元功率反应降低；所有这些缺陷在HCHF饮食下都得到了改善。
这种方法提供了一种对海马神经血管耦合敏感的、无需任务的检测方法。喂食HCHF的TgAD大鼠中神经血管和电生理指标的短暂改善可能是代谢失调的AD大脑从增加的代谢物可用性中获益的一种表现。
基于伪连续动脉自旋标记（pCASL）磁共振成像（MRI）对海马功能性充血的表征。在有症状的阿尔茨海默病（AD）病理中，海马功能性充血减弱。高碳水化合物、高脂肪（HCHF）饮食可短暂恢复有症状AD病理中的海马功能性充血。
