Cerebrospinal fluid fatty acid binding protein 3: A screening biomarker for preclinical Alzheimer’s disease

Abstract

AbstractBackgroundPreclinical Alzheimer’s disease (AD) is a silent, asymptomatic stage of AD, classified into three sub‐stages based on amyloid positivity, neuronal injury and presence of subtle cognitive decline. Pathophysiological biomarkers are needed to effectively screen cases of preclinical AD based on the specific stage. Fatty acid binding protein 3 (FABP3) is a biomarker of neuronal membrane disruption, associated with lipid dyshomeostasis. The current study evaluated the potential of cerebrospinal fluid (CSF) FAPB3, as a stage‐specific screening biomarker of preclinical AD.MethodThe levels of FABP3 were quantified in CSF samples of healthy participants (n = 159) from the Australian Imaging, Biomarkers and Lifestyle studying of ageing (AIBL), on the Meso Scale Discovery platform using Human FABP3 Kit (Meso Scale Diagnostics, USA). A sub‐set of participants, (n = 142) had undergone positron emission tomography (PET) brain amyloid imaging. These participants were dichotomised into PET amyloid positive (n = 49) and negative (n = 93) based on the PET derived standardized uptake value ratio (SUVR) cut‐off of 1.4. Diagnostic differences in CSF FABP3 levels were assessed among amyloid positive and negative participants. Cox proportional hazards model was used to identify individuals likely to progress to an early stage of cognitive impairment, by assessing the risk of conversion from clinical dementia rating (CDR) of 0 to CDR ≥ 0.5. CDR assessments were done over 4.5 years; participants who had at least two follow‐up assessments were included in the analysis.ResultCSF FABP3 levels were significantly higher in PET amyloid positive healthy participants as compared to negatives (p = 0.001). CSF FABP3 levels were significantly higher in healthy participants who converted from CDR 0 to CDR ≥ 0.5, over 4.5 years, against non‐converters (p = 0.039). In an unadjusted analyses, CSF levels of FABP3 significantly predicted the risk of conversion from CDR 0 to CDR ≥ 0.5, with a hazard ratio (HR) of 1.58 (CI 1.03‐2.43, p = 0.035).ConclusionFABP3 is a biomarker of early neurodegenerative changes, which can be used to screen cases of preclinical AD with asymptomatic amyloidosis, as well as identify individuals likely to progress to a clinical stage of AD.