Abstract
OBJECTIVE: Alzheimer disease (AD), a continuous disease spectrum, includes the symptomatic stages of the period of mild cognitive impairment (MCI) and the dementia period, also known as AD dementia. Focusing on MCI and AD dementia screening, i.e., AD spectrum screening, we analyzed the value of plasma biomarkers for diagnosing cognitive dysfunction in the local populations of Deyang City, Sichuan Province, China to provide evidence for the early screening and diagnosis of cognitive dysfunction. METHODS: A questionnaire survey was conducted between August 2023 and October 2023 among people aged 50 years or older in Deyang City, Sichuan Province. The survey covered demographic information, information on medical history, and cognitive function assessment. Subjects with MCI were included in the MCI group, those with AD dementia were included in the AD group, and the others were included in the healthy controls (HC) group. A partial sample, including all patients with AD dementia and a randomized sample of MCI patients and HC, was drawn. Then, the plasma levels of four cognition-related biomarkers, including phosphorylated tau217 (p-tau217), were measured using an ultrasensitive digital chip immunoassay technology independently developed in China. Amyloid beta (Aβ) deposition was determined by positron emission tomography (PET) using Aβ molecular probes in all AD dementia patients and some of the MCI patients. The diagnostic value of the plasma biomarkers for cognitive dysfunction was assessed. RESULTS: A total of 2833 subjects were investigated, including 30 (1.1%) with AD dementia, 437 (15.4%) with MCI, and 2366 (83.5%) with HC. We measured the plasma levels of 4 biomarkers of 30 AD dementia patients, 50 MCI patients, and 35 HC. Plasma p-tau217 performed best in differentiating AD dementia from HC and MCI, with the area under the curve (AUC) of receiver operator characteristic curves being 0.96 (95% CI: 0.91-1.00) and 0.93 (95% CI: 0.87-0.98), respectively. Plasma p-tau217 levels in the AD dementia, MCI, and HC groups were (2.32±1.27), (0.54±0.45), and (0.42±0.19) pg/mL, respectively, and the difference was statistically significant (P<0.0001). A total of 36 patients underwent Aβ PET examination. Plasma p-tau217 showed the best performance in the diagnosis of Aβ deposition (AUC: 0.99, 95% CI: 0.96-1.00). Plasma p-tau217 levels were higher in Aβ-deposition-positive patients ([2.52±1.17] pg/mL) than those in Aβ-deposition-negative patients ([0.53±0.19] pg/mL), and the difference was statistically significant (P<0.0001). Plasma p-tau217 levels were significantly and positively correlated with Aβ PET uptake values in multiple brain regions of the frontal, temporal, and occipital lobes (r>0.70, P<0.0001). CONCLUSION: Plasma biomarkers measured with a technology independently developed in China demonstrate good performance in diagnosing AD dementia. Plasma p-tau217, in particular, demonstrates the highest diagnostic value and can be used for AD dementia screening of large populations.