Barrett-Young Ashleigh, Cawston Erin E, Ryan Brigid, Abraham Wickliffe C, Ambler Antony, Anderson Tim, Cheyne Kirsten, Goodin Elizabeth, Hogan Sean, Houts Renate M, Ireland David, Knodt Annchen R, Kokaua Jesse, Melzer Tracy R, Ramrakha Sandhya, Sugden Karen, Williams Benjamin, Wilson Phillipa, Caspi Avshalom, Hariri Ahmad R, Moffitt Terrie E, Poulton Richie, Theodore Reremoana
Dunedin Multidisciplinary Health & Development Research Unit, Department of Psychology, University of Otago, Dunedin, New Zealand.
Centre for Brain Research, University of Auckland, Auckland, New Zealand.
medRxiv. 2025 Apr 10:2025.04.09.25325556. doi: 10.1101/2025.04.09.25325556.
Although plasma pTau181 has been shown to accurately discriminate patients with Alzheimer's disease from healthy older adults, its utility as a preclinical biomarker in middle-aged community-based cohorts is unclear.
Participants were members of the Dunedin Multidisciplinary Health and Development Study, a longitudinal study of 1037 people born in New Zealand in 1972-1973. Plasma pTau181, MRI-based brain structure, and DunedinPACE (an epigenetic biomarker of biological ageing) were measured at age 45; cognition was measured in childhood and age 45.
We observed a wide range of pTau181 concentrations in our same-aged sample (n=856; M=13.6pg/mL, SD=9.1pg/mL). Males had significantly higher pTau181 concentrations than females. No statistically significant associations were observed with cognitive decline, lower structural brain integrity, or accelerated biological ageing.
In this midlife cohort, wide variation in pTau181 concentrations was present by age 45, but was not associated with patterns of AD-risk in cognition, brain structure, or biological ageing.
尽管血浆pTau181已被证明能准确区分阿尔茨海默病患者与健康老年人，但它作为基于社区的中年队列中的临床前生物标志物的效用尚不清楚。
参与者是达尼丁多学科健康与发展研究的成员，该研究对1972年至1973年在新西兰出生的1037人进行了纵向研究。在45岁时测量血浆pTau181、基于MRI的脑结构和达尼丁PACE（生物衰老的表观遗传生物标志物）；在儿童期和45岁时测量认知能力。
在我们的同龄样本（n = 856；M = 13.6 pg/mL，SD = 9.1 pg/mL）中，我们观察到pTau181浓度范围很广。男性的pTau181浓度显著高于女性。未观察到与认知能力下降、脑结构完整性降低或生物衰老加速有统计学意义的关联。
在这个中年队列中，到45岁时pTau181浓度存在广泛差异，但与认知、脑结构或生物衰老方面的阿尔茨海默病风险模式无关。
