背景:神经退行性病变,包括tau证词,与晚发性抑郁症(LOD)有关,尽管死后发现了脑tau积累,但缺乏体内证据证明迟发性双相情感障碍(LOBD)的神经病理学基础。当前的研究旨在评估LOBD和LOD患者的tau病理,使用18F-florzolotau进行正电子发射断层扫描(PET),用于阿尔茨海默病(AD)和非ADtau原纤维的放射性配体。
方法:我们研究了45岁后首次出现躁狂症或抑郁症的LOBD和LOD患者。LOBD患者21例(68.8±9.6岁,女性11例),LOD患者15例(73.0±5.8岁,女性11例),39名年龄匹配的健康对照(HCs)(67.1±9.1岁;19名女性)接受了18F-florzolotau和11C-PiB的tau和淀粉样蛋白PET扫描,分别。淀粉样蛋白阳性通过11C-PiB-PET图像的视觉读取来确定,通过计算覆盖大脑灰质和基底神经节的52个区域与优化的参考组织的标准化摄取值比率(SUVR)来评估tau沉积。所有SUVR均针对年龄和性别进行校正,并转换为相对于HC的Z评分。根据Z评分≥2.0的区域的存在确定tau病理的阳性和拓扑。
结果:在13LOBD中观察到18F-florzolotau-PET阳性(62%),7LOD(47%),和11例HC(28%)受试者,而4LOBD,4LOD,无HC个体为11C-PiB-PET阳性。tau病变的患病率仅在LOBD和HC之间存在显着差异(P=0.043,经多重比较校正)。11C-PiB-PET阳性AD病理中的Tau拓扑结构主要包括额叶(1个LOBD和3个LOD),颞侧(3LOBD和1LOD),和后(1LOBD)积累。同时,11C-PiB阴性病例的tau病理表现为主要额叶(2LOBD和1LOD),时间(1LOBD和1LOD),后(4LOBD和1LOD),和基底神经节(2LOBD)定位。
结论:我们的研究结果表明,很大一部分LOBD患者的tau病变与各种AD亚型和非ADtau病变相关,表明早期额颞叶变性亚类不同。
BACKGROUND: Neurodegenerative pathologies, including tau depositions, have been implicated in late-onset depression (LOD), while there is a lack of in-vivo evidence for the neuropathological basis of late-onset bipolar disorder (LOBD) despite postmortem findings of cerebral tau accumulations. The current study aimed to assess tau pathologies in LOBD and LOD patients positron emission tomography (PET) with 18F-florzolotau, a radioligand for Alzheimer\'s disease (AD) and non-AD tau fibrils.
METHODS: We studied LOBD and LOD patients who developed the first episode of mania or depression after age 45. Twenty-one patients with LOBD (68.8 ± 9.6 years old; 11 females), 15 patients with LOD (73.0 ± 5.8 years old; 11 females), and 39 age-matched healthy controls (HCs) (67.1 ± 9.1 years old; 19 females) underwent tau and amyloid PET scans with 18F-florzolotau and 11C-PiB, respectively. Amyloid positivity was determined by a visual read of 11C-PiB-PET images, and tau depositions were assessed by calculating standardized uptake value ratios (SUVRs) in 52 regions covering the cerebral grey matter and basal ganglia to the optimized reference tissue. All SUVRs were corrected for age and sex and converted to Z-score relative to HCs. The positivity and topology of tau pathologies were determined according to the presence of a region with a Z-score ≥ 2.0.
RESULTS: 18F-florzolotau-PET positivity was observed in 13 LOBD (62%), 7 LOD (47%), and 11 HC (28%) subjects, whereas 4 LOBD, 4 LOD, and no HC individuals were 11C-PiB-PET-positive. A significant difference in the prevalence of tau pathologies was only found between LOBD and HCs (P = 0.043, corrected for multiple comparisons). Tau topologies in the cases with 11C-PiB-PET-positive AD pathologies consisted of predominant frontal (1 LOBD and 3 LODs), lateral temporal (3 LOBDs and 1 LOD), and posterior (1 LOBD) accumulations. Meanwhile, tau pathologies in 11C-PiB-negative cases showed predominant frontal (2 LOBDs and 1 LOD), temporal (1 LOBD and 1 LOD), posterior (4 LOBDs and 1 LOD), and basal ganglia (2 LOBDs) localizations.
CONCLUSIONS: Our findings suggest that a significant subset of LOBD patients harbor tau lesions linked to various AD subtypes and non-AD tauopathies indicative of distinct early-stage frontotemporal lobar degeneration subcategories.