Journal Home > Volume 7 , Issue 1
Brain Science Advances 2021, 7(1): 44-55 https://doi.org/10.26599/BSA.2021.9050003
Research Article | Open Access | Issue | Published: 05 March 2021

Cerebrospinal fluid heart fatty acid-binding protein as a predictive biomarker of neurodegeneration in Alzheimer’s disease

Show Author's Information Lu Pan1,  Ya-Nan Ou2,  Lin Tan2,  Lan Tan1,2( ),  Jin-Tai Yu3( )
Department of Neurology, Qingdao Municipal Hospital, Dalian Medical University, Dalian 116044, Liaoning, China.
Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao 266071, Shandong, China.
Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China
Keywords:
Alzheimer’s disease, neurodegeneration, cerebrospinal fluid, heart fatty acid-binding protein (HFABP), biomarker
Cite this article:
Pan L, Ou Y-N, Tan L, et al. Cerebrospinal fluid heart fatty acid-binding protein as a predictive biomarker of neurodegeneration in Alzheimer’s disease. Brain Science Advances, 2021, 7(1): 44-55. https://doi.org/10.26599/BSA.2021.9050003
Download citation
EndNote(RIS)
BibTeX

957

Views

88

Downloads

Citations

1

Crossref

N/A

WoS

N/A

Scopus

N/A

CSCD

Abstract Full text About this article
Objective:

This study aims to investigate whether the heart fatty acid-binding protein (HFABP) in the cerebrospinal fluid (CSF) was a potential predictive biomarker for Alzheimer’s disease (AD).

Methods:

We evaluated the associations of CSF HFABP levels with core biomarkers, cognition, and brain structure in a sample population (n = 302) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. Multiple linear regression and mixed-effects models were employed in the analyses. AD progression was assessed using the Kaplan–Meier survival analysis.

Results:

CSF HFABP was higher in patients with mild cognitive impairment and AD than the normal controls (p < 0.001) and was particularly higher in those with amyloid-β (Aβ) pathologic features. CSF HFABP was associated with higher baseline CSF t-tau (p < 0.001), CSF p-tau (p < 0.001), and CSF t-tau/Aβ42 and CSF p-tau/Aβ42 (p < 0.01). Moreover, CSF HFABP was found to play predictive roles in hippocampal atrophy (p < 0.01), cognitive decline (p < 0.05), and the risk of AD (p < 0.001).

Conclusion:

Our findings suggest that CSF HFABP can be a predictive biomarker of AD.


menu
Abstract
Full text
Outline
About this article

Cerebrospinal fluid heart fatty acid-binding protein as a predictive biomarker of neurodegeneration in Alzheimer’s disease

Show Author's information Lu Pan1, Ya-Nan Ou2, Lin Tan2, Lan Tan1,2( ), Jin-Tai Yu3( )
Department of Neurology, Qingdao Municipal Hospital, Dalian Medical University, Dalian 116044, Liaoning, China.
Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao 266071, Shandong, China.
Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China

Abstract

Objective:

This study aims to investigate whether the heart fatty acid-binding protein (HFABP) in the cerebrospinal fluid (CSF) was a potential predictive biomarker for Alzheimer’s disease (AD).

Methods:

We evaluated the associations of CSF HFABP levels with core biomarkers, cognition, and brain structure in a sample population (n = 302) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. Multiple linear regression and mixed-effects models were employed in the analyses. AD progression was assessed using the Kaplan–Meier survival analysis.

Results:

CSF HFABP was higher in patients with mild cognitive impairment and AD than the normal controls (p < 0.001) and was particularly higher in those with amyloid-β (Aβ) pathologic features. CSF HFABP was associated with higher baseline CSF t-tau (p < 0.001), CSF p-tau (p < 0.001), and CSF t-tau/Aβ42 and CSF p-tau/Aβ42 (p < 0.01). Moreover, CSF HFABP was found to play predictive roles in hippocampal atrophy (p < 0.01), cognitive decline (p < 0.05), and the risk of AD (p < 0.001).

Conclusion:

Our findings suggest that CSF HFABP can be a predictive biomarker of AD.

Keywords: Alzheimer’s disease, neurodegeneration, cerebrospinal fluid, heart fatty acid-binding protein (HFABP), biomarker

References(31)

[1]
Moon JH. Endocrine risk factors for cognitive impairment. Endocrinol Metab (Seoul) 2016, 31(2): 185-192.
DOI Google Scholar
[2]
Reitz C. Dyslipidemia and the risk of Alzheimer's disease. Curr Atheroscler Rep 2013, 15(3): 307.
DOI Google Scholar
[3]
Oliveira BCL, Bellozi PMQ, Reis HJ, et al. Inflammation as a possible link between dyslipidemia and Alzheimer's disease. Neuroscience 2018, 376: 127-141.
DOI Google Scholar
[4]
Walter J, van Echten-Deckert G. Cross-talk of membrane lipids and Alzheimer-related proteins. Mol Neurodegener 2013, 8: 34.
DOI Google Scholar
[5]
Baxter LC, Caselli RJ, Johnson SC, et al. Apolipoprotein E epsilon 4 affects new learning in cognitively normal individuals at risk for Alzheimer's disease. Neurobiol Aging 2003, 24(7): 947-52.
DOI Google Scholar
[6]
Lim WL, Martins IJ, Martins RN. The involvement of lipids in Alzheimer's disease. J Genet Genomics 2014, 41(5): 261-274.
DOI Google Scholar
[7]
Bourre JM. Roles of unsaturated fatty acids (especially omega-3 fatty acids) in the brain at various ages and during ageing. J Nutr Health Aging 2004, 8(3): 163-174.
Google Scholar
[8]
Abumrad NA, Ajmal M, Pothakos K, et al. CD36 expression and brain function: does CD36 deficiency impact learning ability? Prostaglandins Other Lipid Mediat. 2005, 77(1-4): 77-83.
DOI Google Scholar
[9]
Veerkamp JH, Zimmerman AW. Fatty acid-binding proteins of nervous tissue. J Mol Neurosci 2001, 16(2/3): 133-42;discussion151–7.
DOI Google Scholar
[10]
Glatz JF, Schaap FG, Binas B, et al. Cytoplasmic fatty acid-binding protein facilitates fatty acid utilization by skeletal muscle. Acta Physiol Scand 2003, 178(4): 367-371.
DOI Google Scholar
[11]
Zimmerman AW, Veerkamp JH. New insights into the structure and function of fatty acid-binding proteins. Cell Mol Life Sci 2002, 59(7): 1096-1116.
DOI Google Scholar
[12]
Olsson B, Hertze J, Ohlsson M, et al. Cerebrospinal fluid levels of heart fatty acid binding protein are elevated prodromally in Alzheimer's disease and vascular dementia. J Alzheimers Dis 2013, 34(3): 673-679.
DOI Google Scholar
[13]
Chiasserini D, Parnetti L, Andreasson U, et al. CSF levels of heart fatty acid binding protein are altered during early phases of Alzheimer's disease. J Alzheimers Dis 2010, 22(4): 1281-1288.
DOI Google Scholar
[14]
Olsson B, Lautner R, Andreasson U, et al. CSF and blood biomarkers for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis. Lancet Neurol 2016, 15(7): 673-684.
DOI Google Scholar
[15]
Desikan RS, Thompson WK, Holland D, et al. Heart fatty acid binding protein and Aβ-associated Alzheimer's neurodegeneration. Mol Neurodegener 2013, 8: 39.
DOI Google Scholar
[16]
Shaw LM, Vanderstichele H, Knapik-Czajka M, et al. Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects. Ann Neurol 2009, 65(4): 403-413.
DOI Google Scholar
[17]
Schindler SE, Gray JD, Gordon BA, et al. Cerebrospinal fluid biomarkers measured by Elecsys assays compared to amyloid imaging. Alzheimers Dement 2018, 11(14), 1460-1469.
DOI Google Scholar
[18]
Crane PK, Carle A, Gibbons LE, et al. Development and assessment of a composite score for memory in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Brain Imaging Behav 2012, 6(4): 502-516.
DOI Google Scholar
[19]
Gibbons LE, Carle AC, Mackin RS, et al. A composite score for executive functioning, validated in Alzheimer's Disease Neuroimaging Initiative (ADNI) participants with baseline mild cognitive impairment. Brain Imaging Behav 2012, 6(4): 517-527.
DOI Google Scholar
[20]
Youden WJ. Index for rating diagnostic tests. Cancer 1950, 3(1): 32-35.
DOI
[21]
Mollenhauer B, Steinacker P, Bahn E, et al. Serum heart-type fatty acid-binding protein and cerebrospinal fluid tau: marker candidates for dementia with Lewy bodies. Neurodegener Dis 2007, 4(5): 366-375.
DOI Google Scholar
[22]
Steinacker P, Mollenhauer B, Bibl M, et al. Heart fatty acid binding protein as a potential diagnostic marker for neurodegenerative diseases. Neurosci Lett 2004, 370(1): 36-39.
DOI Google Scholar
[23]
Cheon MS, Kim SH, Fountoulakis M, et al. Heart type fatty acid binding protein (H-FABP) is decreased in brains of patients with Down syndrome and Alzheimer's disease. J Neural Transm Suppl 2003, 67: 225-234.
DOI Google Scholar
[24]
Mattsson N, Carrillo MC, Dean RA, et al. Revolutionizing Alzheimer's disease and clinical trials through biomarkers. Alzheimers Dement (Amst) 2015, 1(4): 412-419.
DOI Google Scholar
[25]
Vos SJ, Xiong CJ, Visser PJ, et al. Preclinical Alzheimer's disease and its outcome: a longitudinal cohort study. Lancet Neurol 2013, 12(10): 957-965.
DOI Google Scholar
[26]
Jack CR, Knopman DS, Jagust WJ, et al. Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade. Lancet Neurol 2010, 9(1): 119-128.
DOI Google Scholar
[27]
Wang HF, Shen XN, Li JQ, et al. Clinical and biomarker trajectories in sporadic Alzheimer's disease: A longitudinal study. Alzheimers Dement (Amst) 2010, 121(1): e12095.
Google Scholar
[28]
Wunderlich MT, Hanhoff T, Goertler M, et al. Release of brain-type and heart-type fatty acid-binding proteins in serum after acute ischaemic stroke. J Neurol 2005, 252(6): 718-724.
DOI Google Scholar
[29]
Shioda N, Yamamoto Y, Watanabe M, et al. Heart-type fatty acid binding protein regulates dopamine D2 receptor function in mouse brain. J Neurosci 2010, 30(8): 3146-3155.
DOI Google Scholar
[30]
Bjerke M, Zetterberg H, Edman A, et al. Cerebrospinal fluid matrix metalloproteinases and tissue inhibitor of metalloproteinases in combination with subcortical and cortical biomarkers in vascular dementia and Alzheimer's disease. J Alzheimers Dis 2011, 27(3): 665-676.
DOI Google Scholar
[31]
di Paolo G, Kim TW. Linking lipids to Alzheimer's disease: cholesterol and beyond. Nat Rev Neurosci 2011, 12(5): 284-296.
DOI Google Scholar
Publication history
Copyright
Rights and permissions

Publication history

Received: 02 November 2020
Revised: 22 February 2021
Accepted: 28 February 2021
Published: 05 March 2021
Issue date: March 2021

Copyright

© The authors 2021

Rights and permissions

This article is published with open access at journals.sagepub.com/home/BSA

Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/ en-us/nam/open-access-at-sage).

Return