Garrett Liam Rodney, Niccoli Teresa
Genetics, Evolution and Environment Department, Institute of Healthy Ageing, University College London, London, United Kingdom.
Front Neurosci. 2022 Feb 23;16:812222. doi: 10.3389/fnins.2022.812222. eCollection 2022.
Frontotemporal dementia (FTD), hallmarked by antero-temporal degeneration in the human brain, is the second most common early onset dementia. FTD is a diverse disease with three main clinical presentations, four different identified proteinopathies and many disease-associated genes. The exact pathophysiology of FTD remains to be elucidated. One common characteristic all forms of FTD share is the dysregulation of glucose metabolism in patients' brains. The brain consumes around 20% of the body's energy supply and predominantly utilizes glucose as a fuel. Glucose metabolism dysregulation could therefore be extremely detrimental for neuronal health. Research into the association between glucose metabolism and dementias has recently gained interest in Alzheimer's disease. FTD also presents with glucose metabolism dysregulation, however, this remains largely an unexplored area. A better understanding of the link between FTD and glucose metabolism may yield further insight into FTD pathophysiology and aid the development of novel therapeutics. Here we review our current understanding of FTD and glucose metabolism in the brain and discuss the evidence of impaired glucose metabolism in FTD. Lastly, we review research potentially suggesting a causal relationship between FTD proteinopathies and impaired glucose metabolism in FTD.
额颞叶痴呆(FTD)以人脑颞叶前部变性为特征,是第二常见的早发性痴呆。FTD是一种复杂的疾病,有三种主要临床表现、四种已确定的不同蛋白病以及许多与疾病相关的基因。FTD的确切病理生理学仍有待阐明。所有形式的FTD共有的一个共同特征是患者大脑中葡萄糖代谢失调。大脑消耗约占身体能量供应20%的能量,并且主要利用葡萄糖作为燃料。因此,葡萄糖代谢失调可能对神经元健康极为有害。最近,关于葡萄糖代谢与痴呆症之间关联的研究在阿尔茨海默病领域受到关注。然而,FTD也存在葡萄糖代谢失调的情况,不过这在很大程度上仍是一个未被探索的领域。更好地理解FTD与葡萄糖代谢之间的联系可能会进一步深入了解FTD的病理生理学,并有助于开发新的治疗方法。在此,我们综述了目前对FTD和大脑葡萄糖代谢的理解,并讨论了FTD中葡萄糖代谢受损的证据。最后,我们综述了可能表明FTD蛋白病与FTD中葡萄糖代谢受损之间存在因果关系的研究。