Cerebrospinal fluid levels of fatty acid-binding protein 3 are associated with likelihood of amyloidopathy in cognitively healthy individuals

Kunal Dhiman; Victor L Villemagne; Christopher Fowler; Pierrick Bourgeat; Qiao-Xin Li; Steven Collins; Christopher C Rowe; Colin L Masters; David Ames; Kaj Blennow; Henrik Zetterberg; Ralph N Martins; Veer Gupta

doi:10.1002/dad2.12377

Cerebrospinal fluid levels of fatty acid-binding protein 3 are associated with likelihood of amyloidopathy in cognitively healthy individuals

Alzheimers Dement (Amst). 2022 Dec 4;14(1):e12377. doi: 10.1002/dad2.12377. eCollection 2022.

Authors

Kunal Dhiman^{1

2

3}, Victor L Villemagne^{4

5

6}, Christopher Fowler⁷, Pierrick Bourgeat⁸, Qiao-Xin Li⁷, Steven Collins^{6

7}, Christopher C Rowe^{5

6}, Colin L Masters⁷, David Ames^{9

10}, Kaj Blennow^{11

12}, Henrik Zetterberg^{11

12

13

14

15}, Ralph N Martins^{3

16

17

18

19

20}, Veer Gupta^{1

3}

Affiliations

¹ IMPACT - The Institute for Mental and Physical Health and Clinical Translation School of Medicine Deakin University Geelong Victoria Australia.
² Western Health Partnership School of Nursing and Midwifery (Centre for Quality and Patient Safety Research in the Institute of Health Transformation) Faculty of Health Deakin University Melbourne Victoria Australia.
³ School of Medical and Health Sciences Edith Cowan University Joondalup Western Australia Australia.
⁴ Department of Psychiatry University of Pittsburgh Pittsburgh Pennsylvania USA.
⁵ Department of Molecular Imaging & Therapy and Centre for PET Austin Health Heidelberg Victoria Australia.
⁶ Department of Medicine The University of Melbourne Melbourne Victoria Australia.
⁷ The Florey Institute of Neuroscience and Mental Health The University of Melbourne Parkville Victoria Australia.
⁸ Australian e-Health Research Centre CSIRO Health and Biosecurity Brisbane Queensland Australia.
⁹ National Ageing Research Institute Parkville Victoria Australia.
¹⁰ Academic Unit for Psychiatry of Old age St. George's Hospital The University of Melbourne Melbourne Victoria Australia.
¹¹ Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology the Sahlgrenska Academy at the University of Gothenburg Gothenburg Sweden.
¹² Clinical Neurochemistry Laboratory Sahlgrenska University Hospital Gothenburg Sweden.
¹³ Department of Neurodegenerative Disease UCL Queen Square Institute of Neurology London UK.
¹⁴ UK Dementia Research Institute at UCL London UK.
¹⁵ Hong Kong Center for Neurodegenerative Diseases Hong Kong China.
¹⁶ Australian Alzheimer's Research Foundation Ralph and Patricia Sarich Neuroscience Research Institute Nedlands Western Australia Australia.
¹⁷ Department of Biomedical Sciences Macquarie University Sydney New South Wales Australia.
¹⁸ School of Psychiatry and Clinical Neurosciences University of Western Australia Perth Western Australia Australia.
¹⁹ KaRa Institute of Neurological Diseases Sydney New South Wales Australia.
²⁰ Co-operative Research Centre for Mental Health Carlton Victoria Australia.

Abstract

Introduction: Fatty acid-binding protein 3 (FABP3) is a biomarker of neuronal membrane disruption, associated with lipid dyshomeostasis-a notable Alzheimer's disease (AD) pathophysiological change. We assessed the association of cerebrospinal fluid (CSF) FABP3 levels with brain amyloidosis and the likelihood/risk of developing amyloidopathy in cognitively healthy individuals.

Methods: FABP3 levels were measured in CSF samples of cognitively healthy participants, > 60 years of age (n = 142), from the Australian Imaging, Biomarkers & Lifestyle Flagship Study of Ageing (AIBL).

Results: FABP3 levels were positively associated with baseline brain amyloid beta (Aβ) load as measured by standardized uptake value ratio (SUVR, standardized β = 0.22, P = .009) and predicted the change in brain Aβ load (standardized β = 0.32, P = .004). Higher levels of CSF FABP3 (above median) were associated with a likelihood of amyloidopathy (odds ratio [OR] 2.28, 95% confidence interval [CI] 1.12 to 4.65, P = .023).

Discussion: These results support inclusion of CSF FABP3 as a biomarker in risk-prediction models of AD.

Keywords: Alzheimer's disease; amyloid; early diagnosis; risk prediction; screening.