Cerebrospinal fluid levels of fatty acid binding protein 3 associate with brain amyloidosis in cognitively healthy individuals at risk of developing Alzheimer’s disease

Abstract

AbstractBackgroundAn accurate diagnosis of preclinical Alzheimer’s disease (AD) can be made by developing classifier algorithms that include biomarkers commensurate with different pathological changes. Amyloid positivity forms the key criterion of identifying cognitively healthy individuals having either preclinical AD pathological change or preclinical AD. Therefore, biomarkers that not only associate with a specific pathophysiology, but also with brain amyloidosis should be included in diagnostic classifiers. Here, we assessed the association of baseline levels of cerebrospinal fluid (CSF) fatty acid binding protein 3 (FABP3) – a biomarker of neurodegeneration associated with disrupted lipid metabolism, with brain amyloidosis at baseline, as well as change in amyloidosis, in cognitively healthy individuals.MethodFatty acid binding protein 3 levels were measured in CSF samples of 142 cognitively healthy participants from the Australian Imaging, Biomarkers and Lifestyle study of ageing (AIBL), using a commercial electrochemiluminescence immunoassay on a Meso Scale Discovery platform. Participants were aged >60 years, and their brain amyloid‐β (Aβ) load was assessed via positron emission tomography (PET) using different tracers.ResultAssociation of CSF FABP3 levels with baseline brain Aβ load as measured by standardized uptake value ratio (SUVR), as well as change in Aβ load at follow‐up was assessed using linear regression analyses. The average follow‐up time interval was 1.7 years. FABP3 levels were positively associated with baseline brain Aβ load as measured by SUVR (standardised β = 0.22, p = 0.009) and also with the change in brain Aβ load i.e., change in SUVR at follow‐up (standardised β = 0.32, p = 0.004).ConclusionResults indicate that changes in amyloid pathology align with changes in lipid metabolism. Since FABP3 is a biomarker of neurodegeneration, indicative of disrupted lipid metabolism and associated with amyloidosis, it can be used to facilitate screening or diagnosis of preclinical AD.