Reduced Cerebrospinal Fluid Concentration of Apolipoprotein A-I in Patients with Alzheimer’s Disease

Article type: Research Article

Authors: Johansson, Per^{a; b} | Almqvist, Erik G.^c | Bjerke, Maria^d | Wallin, Anders^e | Johansson, Jan-Ove^b | Andreasson, Ulf^{e; f} | Blennow, Kaj^{e; f} | Zetterberg, Henrik^{e; f; g} | Svensson, Johan^{b; c; *}

Affiliations: [a] Department of Neuropsychiatry, Skaraborg Central Hospital, Falköping, Sweden | [b] Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden | [c] Department of Endocrinology, Skaraborg Central Hospital, Skövde, Sweden | [d] Department of Biomedical Sciences, Reference Center for Biological Markers of Dementia, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium | [e] Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden | [f] Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden | [g] Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK

Correspondence: [*] Correspondence to: Dr. Johan Svensson, Institute of Medicine, Gröna Stråket 8, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden. Tel.: +46 31 7411712; Fax: +46 31 821524; E-mail: [email protected].

Abstract: Background:Apolipoprotein E (ApoE) has been extensively studied in Alzheimer’s disease (AD), but little is known of apolipoprotein A-I (ApoA-I) in cerebrospinal fluid (CSF). Objective:Plasma lipids as well as ApoA-I and ApoE in plasma and CSF were determined and related to Mini-Mental State Examination (MMSE) score, APOE genotype, and CSF AD biomarkers. Methods:Consecutive patients with AD (n = 29), stable mild cognitive impairment (n = 13), other dementias (n = 14), and healthy controls (n = 18) were included at a single center. Results:AD patients had higher plasma triglycerides and lower CSF ApoA-I concentration than controls (both p < 0.05). CSF ApoE concentration was reduced in other dementias (p < 0.01). In AD as well as other dementias, the ratios between CSF and plasma concentrations of both ApoA-I and ApoE were lower than those in the controls. ApoA-I and ApoE in plasma and CSF were not influenced by APOE ɛ4 allele distribution. In the total study population (n = 74), CSF ApoA-I correlated positively with MMSE score (r = 0.26, p < 0.05) and negatively with CSF P-tau (r = –0.25, p < 0.05). CSF ApoE correlated positively with CSF concentrations of T-tau and P-tau in the total study population and in AD patients. Conclusion:CSF ApoA-I was reduced in AD patients and associated with measures of cognitive function and AD disease status. The mechanisms underlying the decreased CSF:plasma ratios of ApoA-I and ApoE in AD and other dementias need to be explored in further studies.

Keywords: Alzheimer’s disease, apolipoprotein A-I, apolipoprotein E, cerebrospinal fluid, lipids, other dementia

DOI: 10.3233/JAD-170226

Journal: Journal of Alzheimer's Disease, vol. 59, no. 3, pp. 1017-1026, 2017