Joynes Cassandra M, Bilgel Murat, An Yang, Moghekar Abhay R, Ashton Nicholas J, Kac Przemysław R, Karikari Thomas K, Blennow Kaj, Zetterberg Henrik, Thambisetty Madhav, Ferrucci Luigi, Resnick Susan M, Walker Keenan A
Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, Maryland, USA.
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Alzheimers Dement. 2025 Jan;21(1):e14405. doi: 10.1002/alz.14405. Epub 2024 Nov 28.
The factors that influence the progression of Alzheimer's disease (AD) after individuals become amyloid-positive are poorly understood. This study examines how sex influences the longitudinal trajectories of plasma AD and neurodegenerative biomarkers in the years following a person's estimated onset of amyloid-β.
Linear mixed-effects modeling investigated overall and sex-specific longitudinal trajectories of plasma biomarkers, brain volumes, and cognition relative to the estimated age of amyloid onset in a cohort of 78 amyloid-positive Baltimore Longitudinal Study of Aging (BLSA) participants (n = 45 male; follow-up time: 6.8 years [SD 3.31]). Amyloid status was ascertained with C-Pittsburgh compound B (PiB) PET imaging.
After amyloid onset, men displayed steeper increases in pTau181, pTau231, and neurofilament light (NfL) compared to women. In this same period, men demonstrated steeper declines in brain volume and cognitive performance.
These findings suggest that sex influences the trajectory of AD pathology, neuronal injury, and symptom progression after individuals become amyloid-positive.
Steeper rates of increase in pTau and GFAP among amyloid-positive individuals. After amyloid onset, steeper increases in pTau and NfL concentrations in men than in women. Steeper declines in brain volume and cognition in men corroborate biomarker results.
个体出现淀粉样蛋白阳性后，影响阿尔茨海默病（AD）进展的因素尚不清楚。本研究探讨了性别如何影响个体估计出现淀粉样β蛋白后的几年中血浆AD和神经退行性生物标志物的纵向轨迹。
采用线性混合效应模型，研究了78名淀粉样蛋白阳性的巴尔的摩纵向衰老研究（BLSA）参与者队列（n = 45名男性；随访时间：6.8年[标准差3.31]）中，血浆生物标志物、脑容量和认知相对于估计淀粉样蛋白发病年龄的总体和性别特异性纵向轨迹。淀粉样蛋白状态通过C-匹兹堡化合物B（PiB）PET成像确定。
淀粉样蛋白发病后，与女性相比，男性的pTau181、pTau231和神经丝轻链（NfL）升高更为明显。在同一时期，男性的脑容量和认知能力下降更为明显。
这些发现表明，性别会影响个体出现淀粉样蛋白阳性后的AD病理、神经元损伤和症状进展轨迹。
淀粉样蛋白阳性个体中pTau和GFAP的升高速度更快。淀粉样蛋白发病后，男性的pTau和NfL浓度升高比女性更明显。男性脑容量和认知能力的下降更明显，这证实了生物标志物的结果。
