Clinical Memory Research Unit, Lund University, Lund, Sweden.
Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Amsterdam UMC, Location VUMC, Amsterdam, The Netherlands.
J Nucl Med. 2022 Jun;63(Suppl 1):20S-26S. doi: 10.2967/jnumed.121.263196.
The advent of PET ligands that bind tau pathology has enabled the quantification and visualization of tau pathology in aging and in Alzheimer disease (AD). There is strong evidence from neuropathologic studies that the most widely used tau PET tracers (i.e., F-flortaucipir, F-MK6240, F-RO948, and F-PI2620) bind tau aggregates formed in AD in the more advanced (i.e., ≥IV) Braak stages. However, tracer binding in most non-AD tauopathies is weaker and overlaps to a large extent with known off-target binding regions, limiting the quantification and visualization of non-AD tau pathology in vivo. Off-target binding is generally present in the substantia nigra, basal ganglia, pituitary, choroid plexus, longitudinal sinuses, meninges, or skull in a tracer-specific manner. Most cross-sectional studies use the inferior aspect of the cerebellar gray matter as a reference region, whereas for longitudinal analyses, an eroded white matter reference region is sometimes selected. No consensus has yet been reached on whether to use partial-volume correction of tau PET data. Although an increased neocortical tau PET signal is rare in cognitively unimpaired individuals, even in amyloid-β-positive cases, such a signal holds important prognostic information because preliminary data suggest that an elevated tau PET signal predicts cognitive decline over time. Also, in symptomatic stages of AD (i.e., mild cognitive impairment or AD dementia), tau PET shows great potential as a prognostic marker because an elevated baseline tau PET retention forecasts future cognitive decline and brain atrophy. For differential diagnostic use, the primary utility of tau PET is to differentiate AD dementia from other neurodegenerative diseases, as is in line with the conditions for the approval of F-flortaucipir by the U.S. Food and Drug Administration for clinical use. The differential diagnostic performance drops substantially at the mild-cognitive-impairment stage of AD, and there is no sufficient evidence for detection of sporadic non-AD primary tauopathies at the individual level for any of the currently available tau PET tracers. In conclusion, while the field is currently addressing outstanding methodologic issues, tau PET is gradually moving toward clinical application as a diagnostic and possibly prognostic marker in dementia expert centers and as a tool for selecting participants, assessing target engagement, and monitoring treatment effects in clinical trials.
正电子发射断层扫描（PET）配体与 tau 病理学结合，使 tau 病理学在衰老和阿尔茨海默病（AD）中的定量和可视化成为可能。神经病理学研究有强有力的证据表明，最广泛使用的 tau PET 示踪剂（即 F-flortaucipir、F-MK6240、F-RO948 和 F-PI2620）与 AD 中更高级别（即≥IV 级）Braak 阶段形成的 tau 聚集物结合。然而，在大多数非 AD tau 病中，示踪剂结合较弱，并且在很大程度上与已知的脱靶结合区域重叠，限制了 tau 病在体内的非 AD 病理学的定量和可视化。脱靶结合通常以示踪剂特异性的方式存在于黑质、基底神经节、垂体、脉络丛、纵窦、脑膜或颅骨中。大多数横断面研究使用小脑灰质的下方面作为参考区域，而对于纵向分析，有时选择侵蚀的白质参考区域。目前尚未就是否使用 tau PET 数据的部分容积校正达成共识。虽然在认知正常的个体中，新皮质 tau PET 信号增加很少见，即使在淀粉样蛋白-β阳性的情况下也是如此，但这种信号具有重要的预后信息，因为初步数据表明，tau PET 信号升高可预测随着时间的推移认知能力下降。此外，在 AD 的症状阶段（即轻度认知障碍或 AD 痴呆），tau PET 作为预后标志物具有很大的潜力，因为基线 tau PET 保留率升高预示着未来认知能力下降和脑萎缩。为了进行鉴别诊断，tau PET 的主要用途是将 AD 痴呆与其他神经退行性疾病区分开来，这符合美国食品和药物管理局批准 F-flortaucipir 用于临床使用的条件。在 AD 的轻度认知障碍阶段，其鉴别诊断性能会大幅下降，并且目前尚无足够的证据表明，任何现有的 tau PET 示踪剂都可以在个体水平上检测到散发性非 AD 原发性 tau 病。总之，尽管该领域目前正在解决悬而未决的方法学问题，但 tau PET 正在逐渐作为诊断和可能的预后标志物在痴呆专家中心得到应用，并且作为选择参与者、评估目标参与度和监测临床试验治疗效果的工具。
