Non-linear Character of Plasma Amyloid Beta Over the Course of Cognitive Decline in Alzheimer’s Continuum

Abstract

Plasma amyloid-β (Aβ) was associated with brain Aβ deposition and Alzheimer’s disease (AD) development. However, changes of plasma Aβ over the course of cognitive decline in the Alzheimer’s continuum remained uncertain. We recruited 449 participants to this study, including normal controls (NC), subjective cognitive decline (SCD), mild cognitive impairment (MCI), AD, and non-AD dementia. All the participants underwent plasma Aβ42, Aβ40, and t-tau measurements with single-molecule array (Simoa) immunoassay and PET scan with 18F-florbetapir amyloid tracer. In the subgroup of Aβ-PET positive, plasma Aβ42 and Aβ42/Aβ40 ratio was significantly lower in AD than NC, SCD and MCI, yet SCD had significantly higher levels of plasma Aβ42 than both NC and MCI. In the diagnostic groups of MCI and dementia, participants with Aβ-PET positive had lower plasma Aβ42 and Aβ42/40 ratio than participants with Aβ-PET negative, and the increasing levels of plasma Aβ42 and Aβ42/40 ratio indicated lower risks of Aβ-PET positive. However, in the participants with SCD, plasma Aβ42 and Aβ40 were higher in the subgroup of Aβ-PET positive than Aβ-PET negative, and the increasing levels of plasma Aβ42 and Aβ40 indicated higher risks of Aβ-PET positive. No significant association was observed between plasma Aβ and Aβ-PET status in normal controls. These findings showed that, in the continuum of AD, plasma Aβ42 had a significantly increasing trend from NC to SCD before decreasing in MCI and AD. Furthermore, the predictive values of plasma Aβ for brain amyloid deposition were inconsistent over the course of cognitive decline.

Brain perfusion, cognition, and plasma Alzheimer's biomarkers in moyamoya disease

“…As a new screening strategy, plasma AD biomarkers are reported to have comparable diagnostic efficacy with gold standard methods 25–31 . In a previous study, plasma Aβ42 showed an increasing trend in normal to subjective cognitive decline before decreasing in mild cognitive impairment (MCI) and AD 32 . This reported biphasic change is similar to our results, in which plasma Aβ42 was slightly elevated but not significant in newly diagnosed MMD patients.…”

“…[25][26][27][28][29][30][31] In a previous study, plasma Aβ42 showed an increasing trend in normal to subjective cognitive decline before decreasing in mild cognitive impairment (MCI) and AD. 32 This reported biphasic change is similar to our results, in which plasma Aβ42 was slightly elevated but not significant in newly diagnosed MMD patients.…”

Progress in blood biomarkers of subjective cognitive decline in preclinical Alzheimer's disease

“…Furthermore, the predictive value of plasma Aβ for brain amyloid deposition is inconsistent throughout cognitive decline. [ 35 ] In a retrospective clinical study, lower Aβ40 and Aβ42 levels were associated with more significant cognitive decline, based on the patient's 3-year changes in the Montreal Cognitive Assessment and Cambridge Cognitive Examination. [ 36 ] The significant positive correlation between elevated plasma Aβ levels and improvements in subjective and objective cognitive indicators may reflect a functional relationship similar to that between cerebral Aβ burden and memory complaints and/or cognitive performance in cross-sectional studies of older adults without dementia.…”

“…In the AD continuum, plasma Aβ42 showed a significantly increasing trend from NC to SCD, before decreasing in the MCI and AD stages. Furthermore, the predictive value of plasma Aβ for brain amyloid deposition is inconsistent throughout cognitive decline [35] . In a retrospective clinical study, lower Aβ40 and Aβ42 levels were associated with more significant cognitive decline, based on the patient's 3-year changes in the Montreal Cognitive Assessment and Cambridge Cognitive Examination [36] .…”

Altered limbic functional connectivity in individuals with subjective cognitive decline: Converging and diverging findings across Chinese and German cohorts

“…Accordingly, it is unclear whether the current SCD research definition is equally suited for Eastern populations, or needs tailoring regarding cultural appropriateness and specificity for the target population 7 . To harmonize SCD research across cultures, Sino‐German conferences took place (2016, 2017, 2019), 8 and Chinese SCD cohorts were established using a contemporary SCD research definition 9–12 . Beyond adherence to the general SCD definition, various SCD‐related features 1,2 were coded, and their predictive value for amyloid burden was tested in Chinese SCD subjects 13,14 .…”