Clinical characteristics and biomarker profile in early- and late-onset Alzheimer’s disease: the Shanghai Memory Study
Jie Wu, Jing Wang, Zhenxu Xiao, Jiaying Lu, Xiaoxi Ma, Xiaowen Zhou, Yuhan Wu, Xiaoniu Liang, Li Zheng, Ding Ding, Huiwei Zhang, Yihui Guan, Chuantao Zuo, Qianhua Zhao, , Qianhua Zhao, Chuantao Zuo, Ding Ding, Yihui Guan, Huiwei Zhang, Jiaying Lu, Weiqi Bao, Li Zheng, Xiaoniu Liang, Jing Wang, Zhenxu Xiao, Xiaoxi Ma, Jie Wu, Jie Wang, Xiaowen ZhouAbstract
Early-onset Alzheimer’s disease constitutes ∼5–10% of Alzheimer’s disease. Its clinical characteristics and biomarker profiles are not well documented. To compare the characteristics covering clinical, neuropsychological and biomarker profiles between patients with early- and late-onset Alzheimer’s disease, we enrolled 203 patients (late-onset Alzheimer’s disease = 99; early-onset Alzheimer’s disease = 104) from a Chinese hospital-based cohort, the Shanghai Memory Study. A full panel of plasma biomarkers under the amyloid/tau/neurodegeneration framework including plasma amyloid beta 40, amyloid beta 42, total-tau, neurofilament light chain and phosphorylated tau 181 were assayed using ultra-sensitive Simoa technology. Seventy-five patients underwent an amyloid molecular positron emission tomography scan whereas 43 received comprehensive amyloid, Tau deposition and hypometabolism analysis. Clinical features, plasma and imaging biomarkers were compared cross-sectionally. Compared to those with late-onset Alzheimer’s disease, patients with early-onset Alzheimer’s disease presented more severe impairment in language function, lower frequency of APOE ɛ4 and lower levels of plasma neurofilament light chain (all P < 0.05). The plasma phosphorylated tau 181 concentration and phosphorylated tau 181/amyloid beta 42 ratios were higher in early-onset Alzheimer’s disease than in late-onset Alzheimer’s disease (all P < 0.05). More severe Tau deposition as indicated by 18F-florzolotau binding in the precuneus, posterior cingulate cortex and angular gyrus was observed in the early-onset Alzheimer’s disease group. Plasma phosphorylated tau 181 was associated with earlier age at onset and domain-specific cognitive impairment, especially in patients with early-onset Alzheimer’s disease. We concluded that patients with early-onset Alzheimer’s disease differed from late-onset Alzheimer’s disease in cognitive performance and biomarker profile. A higher burden of pathological tau was observed in early-onset Alzheimer’s disease and was associated with earlier age at onset and more profound cognitive impairment.