Diagnostic Power of 24S-Hydroxycholesterol in Cerebrospinal Fluid: Candidate Marker of Brain Health

Article type: Research Article

Authors: Leoni, Valerio^{a; *} | Solomon, Alina^b | Lövgren-Sandblom, Anita^c | Minthon, Lennart^d | Blennow, Kaj^e | Hansson, Oskar^d | Wahlund, Lars-Olof^b | Kivipelto, Miia^b | Björkhem, Ingemar^c

Affiliations: [a] Laboratory of Clinical Pathology and Medical Genetics, AmadeoLab R17, Foundation IRCCS Institute of Neurology “Carlo Besta”, Milano, Italy | [b] Memory Clinic, Department of Geriatrics, Karolinska University Hospital, Huddinge, Sweden; Aging Research Center and Alzheimer Disease Research Center, Karolinska Institute, Sweden; Department of Neurology, University of Eastern Finland | [c] Department of Laboratory Medicine, Division of Clinical Chemistry, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden | [d] Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden | [e] Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden

Correspondence: [*] Correspondence to: Dr. Valerio Leoni, MD, PhD, Laboratory of Clinical Pathology and Medical Genetics, AmadeoLab R17, Foundation IRCCS Institute of Neurology “Carlo Besta”, Via Celoria 11, 20133 Milano (MI), Italy. Tel.: +39 02 2394 4257; E-mails: [email protected]; [email protected].

Abstract: We evaluated the diagnostic potential of 24S-hydroxycholesterol (24OHC) in cerebrospinal fluid. At a memory clinic, we investigated subjects with subjective cognitive impairment (SCI, n = 33), mild cognitive impairment (MCI) patients (n = 27), MCI patients with later progression into Alzheimer dementia at follow up (n = 10), and patients with AD (n = 24). We also had a control group of healthy volunteers who did not later develop cognitive problems (n = 13). The fraction of the population with pathological levels of 24OHC was 8% in controls, 34% in SCI, 37% in MCI, 80% in MCI with progression, and 42% in AD. The corresponding fractions for T-tau, P-tau, and Aβ42 were lower in the case of SCI and MCI but higher in the case of controls and AD. In case of MCI with progression, the fraction of pathological levels of 24OHC and Aβ42 were 80% and 63% respectively. We also studied a population of old healthy subjects age 75–99 years (n = 25). The fraction of individuals in this population with pathological levels of 24OHC was 0% whereas the fraction of individuals with pathological level of at least one of the other three biomarkers was 40%. The diagnostic power of 24OHC in cerebrospinal fluid seems to be similar to or lower than that of the established biomarkers T-tau, P-tau, and Aβ42 in the diagnosis of established AD. Our data suggest that 24OHC may be more sensitive than the classical biomarkers in an early phase of the neurodegenerative process and a better marker for “brain health” in old age.

Keywords: Aging, ApoE, biomarker, cholesterol, cognitive decline, mass spectrometry, neurodegenerative diseases, oxysterols

DOI: 10.3233/JAD-130035

Journal: Journal of Alzheimer's Disease, vol. 36, no. 4, pp. 739-747, 2013