衰老过程中和阿尔茨海默病连续体中区域 tau 积累的速率：AIBL F-MK6240 PET 研究。

Rates of regional tau accumulation in ageing and across the Alzheimer's disease continuum: an AIBL F-MK6240 PET study.

机构信息

Florey Department of Neurosciences & Mental Health, The University of Melbourne, Parkville, Victoria, 3052, Australia; Department of Molecular Imaging & Therapy, Austin Health, Heidelberg, Victoria, 3084, Australia.

Department of Molecular Imaging & Therapy, Austin Health, Heidelberg, Victoria, 3084, Australia; Health and Biosecurity Flagship, The Australian eHealth Research Centre, Melbourne, Victoria, Australia.

出版信息

EBioMedicine. 2023 Feb;88:104450. doi: 10.1016/j.ebiom.2023.104450. Epub 2023 Jan 27.

DOI:10.1016/j.ebiom.2023.104450

PMID:36709581

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9900352/

Abstract

BACKGROUND

Tau positron emission tomography (PET) imaging enables longitudinal observation of tau accumulation in Alzheimer's disease (AD). F-MK6240 is a high affinity tracer for the paired helical filaments of tau in AD, widely used in clinical trials, despite sparse longitudinal natural history data. We aimed to evaluate the natural history of tau accumulation, and the impact of disease stage and reference region on the magnitude and effect size of regional change.

METHODS

One hundred and eighty-four participants: 89 cognitively unimpaired (CU) beta-amyloid negative (Aβ-), 44 CU Aβ+, 51 cognitively impaired Aβ+ (26 with mild cognitive impairment [MCI] and 25 with dementia) had follow-up F-MK6240 PET for one to four years (median 1.48). Regional standardised uptake value ratios (SUVR) were generated. Two reference regions were examined: cerebellar cortex and eroded subcortical white matter.

FINDINGS

CU Aβ- participants had very low rates of tau accumulation in the mesial temporal lobe (MTL). In CU Aβ+, significantly higher rate of accumulation was seen in the MTL (particularly the amygdala), extending into the inferior temporal lobes. In MCI Aβ+, the rate of accumulation was greatest in the lateral temporal, parietal and lateral occipital cortex, and plateaued in the MTL. Accumulation was global in AD Aβ+, except for a plateau in the MTL. The eroded subcortical white matter reference region showed no significant advantage over the cerebellar cortex and appeared prone to spill-over in AD participants. Data fitting suggested approximately 15-20 years to accumulate tau to typical AD levels.

INTERPRETATION

Tau accumulation occurs slowly. Rates vary according to brain region, disease stage and tend to plateau at high levels. Rates of tau accumulation are best measured in the MTL and inferior temporal cortex in preclinical AD and in large neocortical areas, in MCI and AD.

FUNDING

NHMRC; Cerveau Technologies.

摘要

背景

tau 正电子发射断层扫描（PET）成像使 tau 在阿尔茨海默病（AD）中的积累能够进行纵向观察。F-MK6240 是 AD 中 tau 双螺旋丝的高亲和力示踪剂，尽管纵向自然史数据稀疏，但在临床试验中仍被广泛使用。我们旨在评估 tau 积累的自然史，以及疾病阶段和参考区域对区域变化幅度和效应大小的影响。

方法

184 名参与者：89 名认知正常（CU）β-淀粉样蛋白阴性（Aβ-），44 名 CU Aβ+，51 名认知障碍 Aβ+（26 名轻度认知障碍[MCI]和 25 名痴呆）进行了 1 至 4 年（中位数 1.48 年）的 F-MK6240 PET 随访。生成了区域标准化摄取值比值（SUVR）。检查了两个参考区域：小脑皮质和侵蚀性皮质下白质。

结果

CU Aβ-参与者的内侧颞叶（MTL）tau 积累率非常低。在 CU Aβ+中，MTL（特别是杏仁核）中tau 的积累率显著增加，扩展到下颞叶。在 MCI Aβ+中，外侧颞叶、顶叶和外侧枕叶皮质的积累率最大，并在 MTL 中达到平台期。AD Aβ+中的积累是全球性的，除了 MTL 中的平台期。侵蚀性皮质下白质参考区与小脑皮质相比没有明显优势，并且在 AD 参与者中似乎容易出现溢出。数据拟合表明，大约需要 15-20 年才能积累到典型的 AD 水平。