Uchida Yuto, Nishimaki Kei, Soldan Anja, Pettigrew Corinne, Ho Sara Grace, Moghekar Abhay, Wang Mei-Cheng, Miller Michael I, Albert Marilyn, Oishi Kenichi
Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Alzheimers Dement. 2025 Aug;21(8):e70544. doi: 10.1002/alz.70544.
This study aimed to delineate trajectories of biomarkers-amyloid beta (Aβ), phosphorylated tau, neurodegeneration, and inflammation-and to identify change points along these trajectories.
Longitudinal data were collected over 30 years from 349 cognitively unimpaired individuals enrolled in the Biomarkers for Older Controls at Risk for Dementia study. Piecewise regression models were used to identify change points in cerebrospinal fluid biomarkers, brain magnetic resonance imaging volumes, and a composite measure of global cognition.
Eighty-two participants progressed to mild cognitive impairment or dementia during the follow-up period. Change points were identified in years prior to clinical symptom onset: Aβ at -17.1 years, phosphorylated tau at -15.8 years, neurofilament light chain and whole-brain white matter at -11.6 years, and total ventricles at -9.7 years.
These findings support the temporal sequence proposed by the dynamic biomarker model of Alzheimer's disease and underscore the significance of white matter degeneration as an early marker for disease progression in the pathological cascade.
Data were collected from 349 participants in Biomarkers for Older Controls at Risk for Dementia, a 30-year cohort study. Eighty-two participants progressed to mild cognitive impairment or dementia over an average of 11 to 12 years. Core cerebrospinal fluid biomarkers for Alzheimer's disease began to accelerate 15 to 20 years before clinical onset. Magnetic resonance imaging volumes accelerated with variations across brain structures. Volumetric changes in the white matter and ventricles preceded the hippocampus.
本研究旨在描绘生物标志物——淀粉样β蛋白（Aβ）、磷酸化tau蛋白、神经退行性变和炎症——的变化轨迹，并确定这些轨迹上的变化点。
从349名参与“痴呆风险老年对照生物标志物”研究的认知未受损个体中收集了30年的纵向数据。采用分段回归模型确定脑脊液生物标志物、脑磁共振成像体积和整体认知综合指标的变化点。
82名参与者在随访期间进展为轻度认知障碍或痴呆。在临床症状出现前数年确定了变化点：Aβ为-17.1年，磷酸化tau为-15.8年，神经丝轻链和全脑白质为-11.6年，总脑室为-9.7年。
这些发现支持了阿尔茨海默病动态生物标志物模型提出的时间顺序，并强调了白质变性作为病理级联中疾病进展早期标志物的重要性。
数据来自“痴呆风险老年对照生物标志物”这一30年队列研究中的349名参与者。82名参与者在平均11至12年的时间里进展为轻度认知障碍或痴呆。阿尔茨海默病的核心脑脊液生物标志物在临床发病前15至20年开始加速变化。磁共振成像体积随脑结构不同而加速变化。白质和脑室的体积变化先于海马体。
