Correlation between Cerebrospinal Fluid Core Alzheimer’s Disease Biomarkers and β-Amyloid PET in Chinese Dementia Population

Abstract

The current diagnoses of Alzheimer’s disease (AD) mainly rely on such measures as amyloid-β (Aβ) and tau neuropathology biomarkers in vivo via cerebrospinal fluid (CSF) and positron emission tomography (PET) imaging, which had been systematically studied in Caucasian individuals, whereas diagnostic performances of these approaches in Chinese dementia population still remain unclear. This study investigated the associations between the levels of CSF core AD biomarkers, including phosphorylated tau (p-Tau181), total tau (t-Tau), Aβ42, and Aβ40 measured by the single-molecule array (Simoa) and cerebral Aβ deposition status assessed by 18F-Florbetapir PET (Aβ PET), and evaluated the predictive values of CSF core AD biomarkers in discriminating Aβ PET status in a clinical dementia cohort of the Chinese population, which consisted of patients with mild cognitive impairment (MCI), AD dementia, and non-Alzheimer’s dementia disease (Non-ADD). Global standard uptake value ratios (SUVRs) were calculated by Aβ PET, which was divided into positive (Aβ+) and negative (Aβ−) through visual analysis. CSF p-Tau181 and p-Tau181/t-Tau ratio were positively correlated with the global SUVR, while CSF Aβ42 and Aβ42/Aβ40 ratio were negatively correlated with the global SUVR. CSF Aβ40 has the highest predictive value in discriminating the MCI group from the AD group, while CSF p-Tau181 was applied to discriminate the AD group from the non-ADD group. CSF Aβ42/Aβ40 ratio, as the optimal predictive factor, was combined with APOE ε4 status rather than age and education, which could improve the predictive ability in differentiating the Aβ+ group from the Aβ– group. The results reveal the universal applicability of CSF core AD biomarkers and Aβ PET imaging in Chinese dementia population, which is helpful in clinical practice and drug trials in China.

GSNgene frameshift mutations in Alzheimer’s disease

“…The correlation analysis was carried out, and positive correlation between the CSF GSN level and CSF Aβ42 level was observed (r=0.289, p=0.009; figure 4G ). As CSF Aβ42 level were negatively correlated with the Aβ depositions (assessed by global standardized uptake value ratio (SUVR) of Aβ PET), 25 patients with AD with lower CSF GSN level tended to exhibit lower CSF Aβ42 level and more Aβ depositions, while no association existed in CSF GSN and CSF Aβ40, CSF Aβ42/40, CSF t-tau or CSF p-tau ( figure 4H,I , and online supplemental figure S5A,B ). Besides, the correlation between the plasma GSN and plasma Aβ42 was also analysed, while no significant difference was observed ( online supplemental figure S5C ).…”

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

“…In addition, the changes of these plasma core AD biomarkers were similar to those of CSF AD core biomarkers in both Asian and Western populations. ,, Given that the changes in plasma core AD biomarkers might be derived from those in the central nervous system, the correlation to core AD biomarkers between plasma and CSF was further analyzed. We observed that in terms of P-tau181, T-tau, P-tau181/T-tau ratio, and Aβ42, there existed positive correlations between plasma and CSF, and P-tau181 showed the highest correlation ( r = 0.526), similar to the result of Janelidze et al in a Cohort 2 study ( r = 0.52) .…”

“…14 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, 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).…”

“…Furthermore, we observed that the correlations between plasma P-tau181, P-tau181/T-tau ratio, Aβ42, and Aβ42/Aβ40 ratio with global Aβ deposition quantified by Aβ PET were consistent with previous reports 29−31 and similar to those between CSF and Aβ PET in our previous study. 15 Voxel-wise analysis showed that plasma P-tau181 and P-tau181/T-tau ratio were positively correlated while Aβ42 and Aβ42/Aβ40 ratio were negatively correlated with Aβ accumulation in multiple cortical regions. The finding about the correlation between plasma P-tau181 and Aβ PET demonstrated a link between metabolism of plasma P-tau181 and Aβ aggregation.…”

Effects of mixed metal exposures on MRI diffusion features in the medial temporal lobe

“…As the result of decades of research, a number of fluid-based biomarkers (e.g., Aβ and tau in blood and CSF) have promise of being able to reflect Alzheimer’s-related disease process in clinical practice (Bjorkli et al, 2020; Visser et al, 2022; Xie et al, 2022). These biofluid based biomarkers, however, do not yield brain region-specific information and/or underlying mechanistic data about how some brain regions are more vulnerable to disease processes.…”