Plasma Aβ biomarker associated with cognitive decline in preclinical Alzheimer’s disease

Abstract

AbstractBackgroundUsing immunoprecipitation‐mass spectrometry, we recently developed and validated a plasma composite biomarker for the assessment of Aβ levels. However, as yet, it’s utility to predict clinical and cognitive outcomes remains unclear. This study aimed to examine the relationship between this plasma Aβ composite biomarker and cognitive function in cognitively normal older adults in two independent cohorts.MethodThis is a longitudinal study conducted in two independent cohorts – the Australian imaging, Biomarkers and Lifestyle (AIBL) study and Japan’s National Centre for Geriatrics and Gerontology (NCGG) study. A series of linear mixed models were conducted to determine the relationships between plasma Aβ composite scores and cognitive decline. Cognitively normal (CN) older adults enrolled in the AIBL study (n=156) and the NCGG study (n=57) were included in this analysis. Participants had undergone Aβ neuroimaging using positron emission tomography (PET), cognitive assessments and provided blood samples. We derived a high‐performance plasma Aβ composite biomarker by immunoprecipitation with mass‐spectrometry. The main outcome measures were composites of episodic memory, executive function, language and attention.ResultBoth continuous and categorical measures of the plasma Aβ composite biomarker were significantly related to decline in episodic memory and executive function (Figure 1). The magnitude of effects of the plasma Aβ composite on episodic memory and executive function were comparable to that observed for the effects of PET Aβ levels on these same outcome measures.ConclusionSeveral plasma Aβ biomarkers have been developed, but none have yet been applied to investigate their relationship with cognitive outcomes. Our results have important implications for the use of this biomarker in the detection of at‐risk individuals.