Increased Protein-Conjugated Acrolein and Amyloid-β_40/42 Ratio in Plasma of Patients with Mild Cognitive Impairment and Alzheimer's Disease

Article type: Research Article

Authors: Waragai, Masaaki^{a; 1} | Yoshida, Madoka^{b; 1} | Mizoi, Mutsumi^b | Saiki, Ryotaro^{b; c} | Kashiwagi, Keiko^d | Takagi, Kiyoshi^e | Arai, Hiroyuki^f | Tashiro, Jun^g | Hashimoto, Makoto^h | Iwai, Naomichi^a | Uemura, Kenichi^a | Igarashi, Kazuei^{b; c; *}

Affiliations: [a] Higashi-Matsudo City Hospital, Matsudo, Chiba, Japan | [b] Amine Pharma Research Institute, Innovation Plaza at Chiba University, Chiba, Japan | [c] Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan | [d] Faculty of Pharmacy, Chiba Institute of Science, Choshi, Chiba, Japan | [e] Kashiwatanaka Hospital, Kashiwa, Chiba, Japan | [f] Department of Geriatrics and Gerontology, Division of Brain Sciences, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan | [g] Department of Internal Medicine, Matsudo City Hospital, Matsudo, Chiba, Japan | [h] Division of Sensory and Motor Systems, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan

Correspondence: [*] Correspondence to: Dr. Kazuei Igarashi, Amine Pharma Research Institute, Innovation Plaza at Chiba University, 1-8-15 Inohana, Chuo-ku, Chiba 260-0856, Japan. E-mail: iga16077@faculty.chiba-u.jp.

Note: [1] These authors contributed equally to this work.

Abstract: The objective of this study was to determine whether plasma levels of acrolein, a compound that causes cell damage, and amyloid-β (Aβ) are useful biochemical markers for Alzheimer's disease (AD). The study included 221 elderly subjects divided into 101 non-demented [33 healthy control and 68 non-demented subjects with white matter hyperintensity (nd-WMH)], 50 mild cognitive impairment (MCI), and 70 AD. Increases in both protein-conjugated acrolein (PC-Acro) and Aβ40/42 ratio were observed in MCI and AD patients compared with values in control subjects. When the combined measurements of PC-Acro and Aβ40/42 ratio were evaluated using the median value of the relative risk value for dementia, they were in the order AD (0.98) ≥ MCI (0.97) > nd-WMH (0.83) > control (0.35). The results indicate that measurements of PC-Acro and Aβ40/42 ratio not only detect MCI and AD patients but also nd-WMH subjects. Furthermore, both PC-Acro and Aβ40/42 ratio in plasma for 120 MCI and AD patients were significantly higher than those for 101 control and nd-WMH subjects, indicating that both values become useful biochemical markers for MCI and AD subjects.

Keywords: Alzheimer's disease, amyloid-β, magnetic resonance imaging, plasma biomarker, protein-conjugated acrolein, white matter hyperintensity

DOI: 10.3233/JAD-2012-120253

Journal: Journal of Alzheimer's Disease, vol. 32, no. 1, pp. 33-41, 2012