Bilgel Murat, An Yang, Walker Keenan A, Moghekar Abhay R, Ashton Nicholas J, Kac Przemyslaw R, Karikari Thomas K, Blennow Kaj, Zetterberg Henrik, Jedynak Bruno M, Thambisetty Madhav, Ferrucci Luigi, Resnick Susan M
Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, Maryland, 21224, USA.
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21287, USA.
medRxiv. 2023 Apr 21:2023.01.12.23284439. doi: 10.1101/2023.01.12.23284439.
Understanding longitudinal plasma biomarker trajectories relative to brain amyloid changes can help devise Alzheimer's progression assessment strategies.
We examined the temporal order of changes in plasma amyloid-β ratio (Aβ /Aβ ), glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and phosphorylated tau ratios (p-tau181/Aβ , p-tau231/Aβ ) relative to C-Pittsburgh compound B (PiB) positron emission tomography (PET) cortical amyloid burden (PiB-/+). Participants (n = 199) were cognitively normal at index visit with a median 6.1-year follow-up.
PiB groups exhibited different rates of longitudinal change in Aβ /Aβ (β = 5.41 × 10^ , SE = 1.95 × 10 , p = 0.0073). Change in brain amyloid was correlated with change in GFAP (r = 0.5, 95% CI = [0.26, 0.68]). Greatest relative decline in Aβ /Aβ (-1%/year) preceded brain amyloid positivity onset by 41 years (95% CI = [32, 53]).
Plasma Aβ /Aβ may begin declining decades prior to brain amyloid accumulation, whereas p-tau ratios, GFAP, and NfL increase closer in time.
了解与脑淀粉样蛋白变化相关的纵向血浆生物标志物轨迹有助于制定阿尔茨海默病进展评估策略。
我们研究了血浆淀粉样蛋白-β比值（Aβ42/Aβ40）、胶质纤维酸性蛋白（GFAP）、神经丝轻链（NfL）以及磷酸化tau比值（p-tau181/Aβ42、p-tau231/Aβ42）相对于匹兹堡化合物B（PiB）正电子发射断层扫描（PET）皮质淀粉样蛋白负荷（PiB-/+）变化的时间顺序。参与者（n = 199）在首次就诊时认知正常，中位随访时间为6.1年。
PiB组在Aβ42/Aβ40方面表现出不同的纵向变化率（β = 5.41×10^-3，SE = 1.95×10^-3，p = 0.0073）。脑淀粉样蛋白的变化与GFAP的变化相关（r = 0.5，95%CI = [0.26, 0.68]）。Aβ42/Aβ40的最大相对下降（-1%/年）比脑淀粉样蛋白阳性发作提前41年（95%CI = [32, 53]）。
血浆Aβ42/Aβ40可能在脑淀粉样蛋白积累前数十年就开始下降，而p-tau比值、GFAP和NfL在时间上更接近时增加。
