However, recent evidence suggests that plasma A42/A40 could be the most accurate biomarker in the very early stages of the disease [10, 11, 25, 46], in accordance with previous observations in CSF samples in which A42/A40 was the 1st modified biomarker in the AD continuum [47, 48]
However, recent evidence suggests that plasma A42/A40 could be the most accurate biomarker in the very early stages of the disease [10, 11, 25, 46], in accordance with previous observations in CSF samples in which A42/A40 was the 1st modified biomarker in the AD continuum [47, 48]. this study, we investigated the ability of plasma amyloid-beta (A)42/A40 percentage measured by an antibody-free mass-spectrometric (MS) method, ABtest-MS, to detect early pathological changes of AD. Methods This cohort study included data from your baseline and 2-yr follow-up visits from your Fundaci ACE Healthy Mind Initiative (FACEHBI) study. Plasma A42/A40 was measured with ABtest-MS and compared to 18F-Florbetaben PET as the research standard (cutoff for early amyloid deposition of 13.5 centiloids). Cross-validation was performed in an self-employed DPUK-Korean cohort. Additionally, associations of plasma A42/A40 with episodic memory space overall performance and mind atrophy were assessed. Results The FACEHBI cohort at baseline included 200 healthy individuals with subjective cognitive decrease (SCD), of which 36 (18%) were A-PET positive. Plasma A42/A40 levels were significantly reduced A-PET positive individuals (median [interquartile range, IQR], 0.215 [0.203C0.236]) versus A-PET negative subjects CD6 (median [IQR], 0.261 [0.244C0.279]) (< .001). Plasma A42/A40 was significantly correlated with A-PET levels (rho = ?0.390; < .001) and identified A-PET status with an area under the receiver operating characteristic curve (AUC) of 0.87 (95% confidence interval [CI], 0.80C0.93). A cutoff for the A42/A40 percentage of 0.241 (maximum Youden index) yielded a level of sensitivity of 86.1% and a specificity of 80.5%. These findings were cross-validated in an self-employed DPUK-Korean cohort (AUC 0.86 [95% CI 0.77C0.95]). Lower plasma A42/A40 percentage was associated with worse episodic memory space performance and improved mind atrophy. Plasma A42/A40 at baseline expected clinical conversion to slight cognitive impairment and longitudinal changes in amyloid deposition and mind atrophy at 2-yr follow-up. Conclusions This study suggests that plasma A42/A40, SJA6017 as determined by this MS-based assay, offers potential value as an accurate and cost-effective tool to identify individuals in the earliest phases of AD, supporting its implementation in clinical tests, preventative strategies and medical practice. Supplementary Info The online version contains supplementary material available at 10.1186/s13195-022-01143-z. Keywords: Alzheimers disease, Amyloid, A42/A40, Percentage, Biomarkers, Plasma, Blood biomarkers, Mass spectrometry, Subjective cognitive decrease Background Alzheimers disease (AD) is the most common form of dementia SJA6017 influencing 55 million people worldwide in 2021 [1]. The manifestation of medical symptoms in AD is definitely preceded by a long preclinical phase where cognitively normal individuals present neuropathological changes in the brain. In this context, assisting biomarker info is particularly important to aid analysis and prognosis of at-risk individuals. The earliest pathological hallmark of AD, mind amyloid- (A) deposition, can be reliably recognized by two well-established methods: cerebrospinal fluid (CSF) and positron emission tomography (PET)-centered A actions [2, 3]. However, the widespread implementation of these biomarkers to facilitate patient screening SJA6017 in medical tests or in routine SJA6017 clinical practice is definitely hampered by their invasiveness, costs and limited availability. Therefore, more accessible and cost-effective diagnostic methods, such as blood-based biomarkers, are urgently needed. The reliable measurement of A in plasma results technically challenging due to the low large quantity of the peptides inside a complex matrix such as plasma [4]; consequently, highly sensitive, accurate and powerful assays are desired. In recent years, technological advances possess made possible the accurate and powerful quantification of plasma A40 and A42. Multiple assays, SJA6017 either immunoassays or mass-spectrometry (MS)-centered methods, have proved that plasma A42/A40 percentage is an accurate surrogate biomarker of mind amyloid pathology [5C8]. However, recent round robin studies possess found discrepancies in the quantification of plasma A40 and specially A42 among different assays [9]. In addition, emerging evidence offers suggested that MS-based methods identify mind A deposition more accurately than immunoassays [10C12], probably because.