Clinical characteristics and biomarker profile in early- and late-onset Alzheimer's disease: the Shanghai Memory Study

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.