Flotillin is a Novel Diagnostic Blood Marker of Alzheimer’s Disease

Article type: Research Article

Authors: Abdullah, Mohammad^a | Kimura, Noriyuki^b | Akatsu, Hiroyasu^{c; d} | Hashizume, Yoshio^d | Ferdous, Taslima^a | Tachita, Takuto^e | Iida, Shinsuke^e | Zou, Kun^a | Matsubara, Etsuro^b | Michikawa, Makoto^{a; *}

Affiliations: [a] Department of Biochemistry, Nagoya City University Graduate School of Medical Sciences, Mizuho-cyo, Mizuho-ku, Nagoya, Aichi, Japan | [b] Department of Neurology, Faculty of Medicine, Oita University, Hazama, Yufu, Oita, Japan | [c] Department of Community-based Medical Education, Nagoya City University Graduate School of Medical Sciences, Mizuho-cyo, Mizuho-ku, Nagoya, Aichi, Japan | [d] Institute for Neuropathology, Fukushimura Hospital, Noyori, Toyohashi, Aichi, Japan | [e] Department of Hemotology and Oncology, Nagoya City University Graduate School of Medical Sciences, Mizuho-cyo, Mizuho-ku, Nagoya, Aichi, Japan

Correspondence: [*] Correspondence to: Makoto Michikawa, MD, PhD, Department of Biochemistry, Graduate School of Medical Sciences, Nagoya City University, Kawasumi 1, Mizuho-cyo, Mizuho-ku, Nagoya 467-8601, Aichi, Japan. Tel.: +81 52 853 8139; Fax: +81 52 841 3480; E-mail: [email protected].

Abstract: Currently, best-characterized indicators for Alzheimer’s disease (AD) diagnosis are the decreased levels of amyloid-β protein 42 and increased levels of phosphorylated tau in cerebrospinal fluid (CSF). The positron emission tomography (PET) imaging with Pittsburgh compound B (PiB) is also used in AD diagnosis by visualizing amyloid deposition in the brain. These methods are invasive or expensive; therefore, less invasive and easily detectable blood biomarkers are required. Because our previous study showed that flotillin release, a marker of exosomes, was attenuated by Aβ, we designed the present study to determine whether flotillin level could be reduced in CSF and/or serum of patients with AD. In this study, we analyzed flotillin levels in CSF and serum of non-AD controls, patients with AD and mild cognitive impairment (MCI) by western blotting. Flotillin levels in cerebroventricular fluid (CVF) and serum of AD, vascular dementia (VaD), and non-AD autopsy cases were also analyzed. Flotillin levels significantly decreased in the CSF and serum of AD patients compared with those of non-AD controls, respectively. Moreover, in patients with MCI due to AD determined by PiB-PET, CSF and serum flotillin levels significantly decreased compared with those of patients with MCI due to non-AD. Flotillin levels remained unchanged in CVF and serum of autopsy cases diagnosed as VaD. Serum flotillin level is negatively associated with brain amyloid deposition indicated as PiB uptake. These results demonstrate that serum flotillin level can serve as one of the blood markers for estimation of brain amyloid deposition and early diagnosis of AD.

Keywords: Alzheimer’s disease, blood diagnostic marker, cerebrospinal fluid, cerebroventricular fluid, flotillin, mild cognitive impairment

DOI: 10.3233/JAD-190908

Journal: Journal of Alzheimer's Disease, vol. 72, no. 4, pp. 1165-1176, 2019