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Introduction:To test the utility of the "A/T/N" system in the Chinese population, we study core Alzheimer's disease (AD) biomarkers in a newly established Chinese cohort.Methods: A total of 411 participants were selected, including 96 cognitively normal individuals, 94 patients with mild cognitive impairment (MCI) patients, 173 patients with AD, and 48 patients with non-AD dementia. Fluid biomarkers were measured with single molecule array. Amyloid beta (Aβ) deposition was determined by 18 F-Flobetapir positron emission tomography (PET), and brain atrophy was quantified using magnetic resonance imaging (MRI).Results: Aβ42/Aβ40 was decreased, whereas levels of phosphorylated tau (p-tau) were increased in cerebrospinal fluid (CSF) and plasma from patients with AD. CSF Aβ42/Aβ40, CSF p-tau, and plasma p-tau showed a high concordance in discriminating between AD and non-AD dementia or elderly controls. A combination of plasma p-tau, apolipoprotein E (APOE) genotype, and MRI measures accurately predicted amyloid PET status.Discussion: These results revealed a universal applicability of the "A/T/N" framework in a Chinese population and established an optimal diagnostic model consisting of costeffective and non-invasive approaches for diagnosing AD.

Loss of function mutations in the progranulin (PGRN) gene is a risk factor for Alzheimer's disease (AD). Previous works reported that the deficiency of PGRN accelerates βamyloid (Aβ) accumulation in AD transgenic mouse brains while overexpression of PGRN could restrain disease progression. However, mechanisms of PGRN in protecting against Aβ deposition remains unclear. Here, using the 5xFAD AD mouse model, we show that intrahippocampal injection of PGRN protein leads to a reduction of Aβ plaques, downregulation of beta-secretase 1 (BACE1), and enhanced microglia Aβ phagocytosis in the mouse hippocampus. Furthermore, PGRN treatment inhibited BACE1 expression in N2a cells and primary culture neurons and improved the phagocytic capacity of microglia isolated from 5xFAD mouse brains. Collectively, our results provide further evidence that enhancing progranulin could be a promising option for AD therapy.