Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan.
Department of Neurology, Keio University School of Medicine, Tokyo, Japan.
Neuropsychopharmacol Rep. 2022 Dec;42(4):437-448. doi: 10.1002/npr2.12281. Epub 2022 Jul 17.
Alzheimer's disease (AD) is the most common cause of dementia worldwide. In AD, abnormal tau accumulates within neurons of the brain, facilitated by extracellular β-amyloid deposition, leading to neurodegeneration, and eventually, cognitive impairment. As this process is thought to be irreversible, early identification of abnormal tau in the brain is crucial for the development of new therapeutic interventions.
F-PI-2620 is one of the second-generation tau PET tracers with presumably less off-target binding than its predecessors. Although a few clinical studies have recently reported the use of F-PI-2620 tau PET in patients with AD, its applicability to AD is yet to be thoroughly examined.
In the present pilot study, we performed F-PI-2620 tau PET in seven cases of probable AD (AD group) and seven healthy controls (HC group). Standardized uptake value ratios (SUVR) in regions of interest (ROIs) in the medial temporal region and neocortex were compared between the AD and HC groups. Furthermore, correlations between regional SUVR and plasma p-tau181 as well as cognitive test scores were also analyzed.
The uptake of F-PI-2620 was distinctly increased in the AD group across all the ROIs. SUVR in all the target ROIs were significantly correlated with plasma p-tau181 levels, as well as with MMSE and ADAS-cog scores.
DISCUSSION & CONCLUSION: Our results add to accumulating evidence suggesting that F-PI-2620 is a promising tau PET tracer that allows patients with AD to be distinguished from healthy controls, although a study with a larger sample size is warranted.
阿尔茨海默病(AD)是全球最常见的痴呆症病因。在 AD 中,异常的 tau 蛋白在大脑神经元内积聚,这一过程由细胞外β-淀粉样蛋白沉积所促进,导致神经退行性变,并最终导致认知障碍。由于该过程被认为是不可逆转的,因此尽早在大脑中发现异常的 tau 蛋白对于开发新的治疗干预措施至关重要。
F-PI-2620 是第二代 tau PET 示踪剂之一,与前体相比,其非靶标结合可能较少。尽管最近有几项临床研究报告了 F-PI-2620 tau PET 在 AD 患者中的应用,但 AD 的适用性尚未得到彻底研究。
在本初步研究中,我们对七例可能患有 AD(AD 组)的患者和七名健康对照者(HC 组)进行了 F-PI-2620 tau PET。比较了 AD 组和 HC 组内侧颞区和新皮质感兴趣区(ROI)的标准化摄取值比(SUVR)。此外,还分析了区域 SUVR 与血浆 p-tau181 以及认知测试评分之间的相关性。
F-PI-2620 在 AD 组的所有 ROI 中的摄取均明显增加。所有靶标 ROI 的 SUVR 均与血浆 p-tau181 水平以及 MMSE 和 ADAS-cog 评分显著相关。
我们的结果增加了越来越多的证据,表明 F-PI-2620 是一种有前途的 tau PET 示踪剂,可将 AD 患者与健康对照者区分开来,尽管需要更大样本量的研究来证实这一结果。