Early Clinical Development, Genentech, Inc., South San Francisco, CA, USA.
Early Clinical Development, Genentech, Inc., South San Francisco, CA, USA.
Neurobiol Aging. 2019 Sep;81:138-145. doi: 10.1016/j.neurobiolaging.2019.05.026. Epub 2019 Jun 6.
The regional relationships between tau positron emission tomography (PET) imaging and cognitive impairment in Alzheimer's disease (AD) remain uncertain. We examined cross-sectional associations between cognitive performance, cerebral uptake of the novel tau PET tracer [F]GTP1, and other neuroimaging indices ([F]florbetapir amyloid PET, magnetic resonance imaging) in 71 participants with normal cognition, prodromal AD, or AD dementia. Greater [F]GTP1 uptake was seen with increasing clinical severity and correlated with poorer cognition. [F]GTP1 uptake and cortical volume (but not [F]florbetapir uptake) were independently associated with cognitive performance, particularly within the temporal lobe. Delayed memory was more specifically associated with temporal [F]GTP1 uptake; other domains correlated with a broader range of regional [F]GTP1 uptake. These data confirm that [F]GTP1 tau PET uptake significantly correlates with cognitive performance in AD, but regional correlations between performance in non-memory cognitive domains were less specific than reported by tau PET imaging studies that included participants with atypical focal cortical AD syndromes. Tau PET imaging may have utility as a surrogate biomarker for clinical AD progression in therapeutic trials of disease-modifying interventions.
tau 正电子发射断层扫描(PET)成像与阿尔茨海默病(AD)认知障碍之间的区域关系仍不确定。我们研究了 71 名认知正常、前驱 AD 或 AD 痴呆患者的认知表现、新型 tau PET 示踪剂 [F]GTP1 的大脑摄取以及其他神经影像学指标([F]florbetapir 淀粉样蛋白 PET、磁共振成像)之间的横断面相关性。随着临床严重程度的增加,[F]GTP1 摄取增加,并与认知能力下降相关。[F]GTP1 摄取和皮质体积(但不是 [F]florbetapir 摄取)与认知表现独立相关,尤其是在颞叶。延迟记忆与颞叶 [F]GTP1 摄取更密切相关;其他领域与更广泛的区域 [F]GTP1 摄取相关。这些数据证实,[F]GTP1 tau PET 摄取与 AD 患者的认知表现显著相关,但与包括非典型局灶性皮质 AD 综合征患者在内的 tau PET 成像研究报告的认知表现之间的区域相关性不太特异。tau PET 成像可能作为疾病修饰干预治疗试验中临床 AD 进展的替代生物标志物具有一定的应用价值。