From the Department of Neurology, Alzheimer Center Amsterdam (J.R., P.S., F.B., R.O.), and Department of Radiology and Nuclear Medicine (L.C.), Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; Department of Health Technologies (J.R.), Tallinn University of Technology; Radiology Centre (J.R.), North Estonia Medical Centre, Tallinn, Estonia; and Clinical Memory Research Unit (R.O.), Lund University, Sweden.
Neurology. 2020 Nov 10;95(19):e2648-e2657. doi: 10.1212/WNL.0000000000010739. Epub 2020 Sep 10.
To investigate the association between discordant β-amyloid (Aβ) PET and CSF biomarkers at baseline and the emergence of tau pathology 5 years later.
We included 730 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants without dementia (282 cognitively normal, 448 mild cognitive impairment) with baseline [F]florbetapir PET and CSF Aβ available. Aβ CSF/PET status was determined at baseline using established cutoffs. Longitudinal data were available for [F]florbetapir (Aβ) PET (baseline to 4.3 ± 1.9 years), CSF (p)tau (baseline to 2.0 ± 0.1 years), cognition (baseline to 4.3 ± 2.0 years), and [F]flortaucipir (tau) PET (measured 5.2 ± 1.2 years after baseline to 1.6 ± 0.7 years later). We used linear mixed modeling to study the association between Aβ CSF/PET status and tau pathology measured in CSF or using PET. We calculated the proportion of CSF+/PET- participants who during follow-up (1) progressed to Aβ CSF+/PET+ or (2) became tau-positive based on [F]flortaucipir PET.
Aβ CSF+/PET+ (n = 318) participants had elevated CSF (p)tau levels and worse cognitive performance at baseline, while CSF+/PET- (n = 80) participants were overall similar to the CSF-/PET- (N = 306) group. Five years after baseline, [F]flortaucipir PET uptake in the CSF+/PET- group (1.20 ± 0.13) did not differ from CSF-/PET- (1.18 ± 0.08, = 0.69), but was substantially lower than CSF+/PET+ (1.48 ± 0.44, < 0.001). Of the CSF+/PET- participants, 21/64 (33%) progressed to Aβ CSF+/PET+, whereas only one (3%, difference < 0.05) became tau-positive based on [F]flortaucipir PET.
Aβ load detectable by both CSF and PET seems to precede substantial tau deposition. Compared to participants with abnormal Aβ levels on both PET and CSF, the CSF+/PET- group has a distinctly better prognosis.
研究基线时β-淀粉样蛋白（Aβ）正电子发射断层扫描（PET）与脑脊液生物标志物不一致，以及 5 年后出现 tau 病理学之间的关系。
我们纳入了 730 名无痴呆的阿尔茨海默病神经影像学倡议（ADNI）参与者（282 名认知正常，448 名轻度认知障碍），这些参与者在基线时具有[F]florbetapir PET 和 CSF Aβ 可用。使用既定的截止值确定基线时 Aβ CSF/PET 状态。纵向数据可用于[F]florbetapir（Aβ）PET（基线至 4.3±1.9 年）、CSF（p）tau（基线至 2.0±0.1 年）、认知（基线至 4.3±2.0 年）和[F]flortaucipir（tau）PET（在基线后 5.2±1.2 年测量，1.6±0.7 年后再次测量）。我们使用线性混合模型研究 Aβ CSF/PET 状态与 CSF 或使用 PET 测量的 tau 病理学之间的关系。我们计算了 CSF+/PET-参与者在随访期间（1）进展为 Aβ CSF+/PET+或（2）基于[F]flortaucipir PET 呈 tau 阳性的比例。
Aβ CSF+/PET+（n=318）参与者基线时有较高的 CSF（p）tau 水平和较差的认知表现，而 CSF+/PET-（n=80）参与者总体上与 CSF-/PET-（n=306）组相似。在基线后 5 年，CSF+/PET-组的[F]flortaucipir PET 摄取量（1.20±0.13）与 CSF-/PET-组（1.18±0.08，=0.69）无差异，但明显低于 CSF+/PET+组（1.48±0.44，<0.001）。CSF+/PET-组的 64 名参与者中有 21 名（33%）进展为 Aβ CSF+/PET+，而仅有 1 名（3%，差异<0.05）基于[F]flortaucipir PET 呈 tau 阳性。
通过 CSF 和 PET 均可检测到的 Aβ 负荷似乎先于大量 tau 沉积。与 PET 和 CSF 上均存在异常 Aβ 水平的参与者相比，CSF+/PET-组的预后明显更好。
