Distinction between mild cognitive impairment and Alzheimer's disease by CSF amyloid β40 and β42, and protein-conjugated acrolein

Mutsumi Mizoi; Madoka Yoshida; Ryotaro Saiki; Masaaki Waragai; Kenichi Uemura; Hiroyasu Akatsu; Keiko Kashiwagi; Kazuei Igarashi

doi:10.1016/j.cca.2014.01.007

Distinction between mild cognitive impairment and Alzheimer's disease by CSF amyloid β40 and β42, and protein-conjugated acrolein

Clin Chim Acta. 2014 Mar 20:430:150-5. doi: 10.1016/j.cca.2014.01.007. Epub 2014 Feb 6.

Authors

Mutsumi Mizoi¹, Madoka Yoshida¹, Ryotaro Saiki², Masaaki Waragai³, Kenichi Uemura³, Hiroyasu Akatsu⁴, Keiko Kashiwagi⁵, Kazuei Igarashi⁶

Affiliations

¹ Amine Pharma Research Institute, Innovation Plaza at Chiba University, Chiba, Japan.
² Amine Pharma Research Institute, Innovation Plaza at Chiba University, Chiba, Japan; Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.
³ Higashi-Matsudo Municipal Hospital, Matsudo, Chiba, Japan.
⁴ Choju Medical Institute, Fukushimura Hospital, Aichi, Japan.
⁵ Faculty of Pharmacy, Chiba Institute of Science, Choshi, Chiba, Japan.
⁶ Amine Pharma Research Institute, Innovation Plaza at Chiba University, Chiba, Japan; Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan. Electronic address: iga16077@faculty.chiba-u.jp.

PMID: 24508996
DOI: 10.1016/j.cca.2014.01.007

Abstract

Background: We found previously that the amyloid β40/42 (Aβ40/42) ratio and the level of protein-conjugated acrolein (PC-Acro) in plasma were increased in mild cognitive impairment (MCI) and Alzheimer's disease (AD) subjects. We determined whether MCI and AD subjects can be differentiated based on the levels of Aβ40, Aβ42, and PC-Acro in cerebrospinal fluid (CSF).

Methods: Aβ40, Aβ42, PC-Acro, Tau and phosphorylated Tau in CSF were measured by ELISA.

Results: Median values of Aβ40, Aβ40/PC-Acro and Aβ40/42 in CSF were significantly lower in 54 AD subjects than those in 40 MCI subjects. Severity of VOI (volume of interest) atrophy was most intensely correlated with the decrease in Aβ40/PC-Acro and then that in Aβ40 and Aβ42/PC-Acro. MMSE was most intensely correlated with the decrease in Aβ42 and Aβ40, and then that in Aβ42/PC-Acro and Aβ40/PC-Acro.

Conclusion: A decrease in Aβ40/PC-Acro in CSF is well correlated with brain damage, and a decrease in Aβ42 and Aβ40 is well correlated with cognitive ability. Measurement of PC-Acro together with Aβ40 and Aβ42 provides a more precise evaluation of severity of AD subjects.

Keywords: Alzheimer's disease; CSF Amyloid-β; MCI; MMSE; Magnetic resonance imaging; Protein-conjugated acrolein.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acrolein / cerebrospinal fluid*
Aged
Aged, 80 and over
Alzheimer Disease / cerebrospinal fluid*
Alzheimer Disease / diagnosis
Amyloid beta-Peptides / cerebrospinal fluid*
Cognitive Dysfunction / cerebrospinal fluid*
Cognitive Dysfunction / diagnosis
Enzyme-Linked Immunosorbent Assay
Female
Humans
Male
Peptide Fragments / cerebrospinal fluid*

Substances

Amyloid beta-Peptides
Peptide Fragments
amyloid beta-protein (1-40)
amyloid beta-protein (1-42)
Acrolein