A combination model of AD biomarkers revealed by machine learning precisely predicts Alzheimer's dementia: China Aging and Neurodegenerative Initiative (CANDI) study

Abstract

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.

Elevation of plasma phosphorylated tau181 during neurological illnesses affecting consciousness and kidney dysfunction

“…While our data may raise more questions than answers, we believe that further research can address the mechanistic view that is crucial for CNS biomarkers. Moreover, it is one of the few studies that describe plasma AD biomarkers in populations of Asian ancestry, 14 , 15 and the first in Thailand. Racial disparity in AD research remains problematic and will obstruct generalization to the underrepresented population.…”

Plasma Core Alzheimer’s Disease Biomarkers Predict Amyloid Deposition Burden by Positron Emission Tomography in Chinese Individuals with Cognitive Decline

“…CANDI launched in 2018 planned to enroll 500 participants for longitudinal study imaging and biochemical biomarkers of precise and early diagnosis of AD among Han Chinese. The detailed inclusion criteria and recruitment procedure for CANDI have been announced . Those with such causes of cognitive dysfunction such as brain infection, hypoxic cerebral damage, epilepsy, stroke, cerebral tumors, acquired immune deficiency syndrome, alcoholism, head trauma, and severe psychiatric diseases were excluded from the recruitment.…”

“…However, fewer systematic and comprehensive research studies have been done to explore the relationship between plasma and CSF core AD biomarkers, including P-tau181, total tau (T-tau), Aβ42, and Aβ40, as well as the predicative efficiency of plasma core AD biomarkers in assessing cerebral Aβ deposition burden performed by Aβ PET in a Chinese dementia population. We reported earlier that CSF core AD biomarkers were associated with the cerebral Aβ deposition status examined by 18 F-florbetapir PET and that the CSF Aβ42/Aβ40 ratio was an optimal predictive factor for evaluating the cerebral Aβ deposition status in the Chinese cognitive decline cohort, a part of the China Aging and Neurodegenerative Disorder Initiative (CANDI) cohort …”

“…Methods for the detection of core AD biomarkers, such as tau and Aβ in plasma, have been made available. Several studies reported that higher plasma phosphorylated tau (P-tau181) and lower plasma Aβ42 or plasma Aβ42/40 ratio were associated with the risk of AD. − Similarly, a recent study found that plasma P-tau181 had the greatest potential for identifying patients with cognitive impairment based on a Chinese population . In addition, the study by Karikari et al showed that increased concentrations of plasma P-tau181 were correlated with high amyloid deposition estimated by 18 F-florbetapir PET .…”

“…We reported earlier that CSF core AD biomarkers were associated with the cerebral Aβ deposition status examined by 18 F-florbetapir PET and that the CSF Aβ42/Aβ40 ratio was an optimal predictive factor for evaluating the cerebral Aβ deposition status in the Chinese cognitive decline cohort, 15 a part of the China Aging and Neurodegenerative Disorder Initiative (CANDI) cohort. 12 In the current study, we further expanded our cohort, which now consisted of cognitively normal (CN), mild cognitive impairment (MCI), AD dementia, and non-Alzheimer's dementia (Non-ADD), and collected the results of plasma and CSF AD core biomarkers measured by ultrasensitive technology (single-molecule array, Simoa). The average sensitivity in such a platform versus conventional ELISA was improved >1200-fold, with coefficients of variation of <10%.…”