Affiliations: [a] Department of Biochemistry, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya, Aichi, Japan
| [b]
Food Ingredients and Technology Institute, Morinaga Milk Industry Co, Ltd. Zama, Kanagawa, Japan
Correspondence:
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Correspondence to: Makoto Michikawa, MD, PhD and Cha-Gyun Jung, PhD, Department of Biochemistry, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku Nagoya 467-8601 Aichi, Japan. Tel.: +81 52 853 8139/Fax: +81 52 841 3480; E-mail: [email protected]. (Makoto Michikawa); Tel.: +81 52 853 8141/Fax: +81-52-841-3480; E-mail: [email protected]. (Cha-Gyun Jung).
Abstract: Lactoferrin (LF) is present in senile plaques and neurofibrillary tangles in the brains of Alzheimer’s disease (AD) patients and amyloid-β protein precursor transgenic (AβPP-Tg) mice. LF has anti-inflammatory and antioxidant functions, which exert neuroprotective effects against AD. However, its effects on memory impairment and AD pathogenesis have not been fully examined. In this study, we examined the effects of LF on memory impairment and AD pathogenesis in AβPP-Tg mice (J20 mice). Nine-month-old J20 mice were fed with control, 2% lactoferrin-containing (LF), and 0.5% pepsin-hydrolyzed lactoferrin-containing (LF-hyd) diets for 3 months. We found that both the LF and LF-hyd diets attenuated memory impairment in J20 mice and decreased brain Aβ40 and Aβ42 levels through the inhibition of amyloidogenic processing of AβPP, as it decreased β-site amyloid protein precursor cleaving enzyme 1 (BACE1) levels. Furthermore, we found for the first time that LF and LF-hyd treatments increased both ApoE secretion and ATP-binding cassette A1 (ABCA1) protein levels in the brains of J20 mice and in primary astrocyte cultures. Moreover, LF and LF-hyd promoted extracellular degradation of Aβ in primary astrocyte cultures. These findings indicate that the reduction in Aβ levels in the brains of mice fed with both the LF and LF-hyd diets may also be mediated by increased ApoE secretion and ABCA1 protein levels, which in turn leads to the enhanced degradation of Aβ in the brains of J20 mice. Our findings suggest that LF and LF-hyd can be used for the treatment and/or prevention of the development of AD.
