Cerebrospinal Fluid Levels of Heart Fatty Acid Binding Protein are Elevated Prodromally in Alzheimer's Disease and Vascular Dementia

Article type: Research Article

Authors: Olsson, Bob^{a; *} | Hertze, Joakim^e | Ohlsson, Mattias^f | Nägga, Katarina^e | Höglund, Kina^b | Basun, Hans^c | Annas, Peter^b | Lannfelt, Lars^c | Andreasen, Niels^d | Minthon, Lennart^e | Zetterberg, Henrik^{a; g} | Blennow, Kaj^a | Hansson, Oskar^e

Affiliations: [a] Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden | [b] AstraZeneca R&D, Södertälje, Sweden | [c] Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden | [d] Memory Clinic, M51, Department of Geriatric Medicine, Karolinska University Hospital, Huddinge, Stockholm, Sweden | [e] Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden | [f] Computational Biology and Biological Physics, Lund University, Lund, Sweden | [g] UCL Institute of Neurology, Queen Square, London, UK

Correspondence: [*] Correspondence to: Bob Olsson, Department of Psychiatry and Neurochemistry, University of Gothenburg. V-house, Sahlgrenska University Hospital Mölndal, 431 80 Mölndal, Sweden. Tel.: +46 31 343 24 06; Fax: +46 31 343 24 26; E-mail: [email protected].

Abstract: Heart fatty acid binding protein (HFABP) is expressed in the brain and is elevated in cerebrospinal fluid (CSF) from patients with several forms of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease with dementia, Lewy body dementia, vascular dementia (VaD), and Creutzfeldt-Jakob disease. However, whether HFABP in CSF is a stable biomarker or if it can help predict conversion from mild cognitive impairment (MCI) to AD or VaD has not been well studied. To address the role of HFABP in neurodegeneration, we analyzed CSF levels of HFABP in 96 AD patients and 65 controls and also in 170 patients with MCI with an average follow up time of 5.7 years. For the stability analysis, two CSF samples were collected from 52 AD patients with a six month interval in between. HFABP levels in CSF were very stable over the six month period (r = 0.93, p < 0.001). Furthermore, the CSF levels of HFABP were significantly elevated in AD compared with controls after adjustments for age and gender (p < 0.001). They were also elevated in the patients with MCI that subsequently converted to AD or VaD compared with those that remained stable (p < 0.001 and p < 0.05, respectively). However, ROC curve analysis showed that HFABP had lesser predictive value in determining conversion from MCI to AD and VaD than Aβ42, t-tau, and p-tau. In conclusion, HFABP seems to be a stable CSF biomarker that reflects neuronal cell death in several neurodegenerative disorders, including early stages of AD and VaD.

Keywords: Alzheimer's disease, biomarker, cerebrospinal fluid, dementia, HFABP, vascular dementia

DOI: 10.3233/JAD-121384

Journal: Journal of Alzheimer's Disease, vol. 34, no. 3, pp. 673-679, 2013