Macrophage colony stimulating factor is associated with excretion of amyloid-[beta] peptides from cerebrospinal fluid to peripheral blood

• Published in: Psychogeriatrics 2008-12, Vol.8 (4), p.188
• Main Authors: JIANG, Jingwei, OKOCHI, Masayasu, TAGAMI, Shinji, NISHITOMI, Kouhei, YANAGIDA, Kanta, NAKAYAMA, Taisuke, TATSUMI, Shin-ichi, MORI, Kohji, TAKEDA, Masatoshi
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Body fluids; Brain; Geriatrics; Peptides
• ISSN: 1346-3500; 1479-8301
• DOI: 10.1111/j.1479-8301.2008.00259.x

Background: The process of aggregation of brain amyloid-[beta] peptides (A[beta]) is thought to be associated with the pathogenesis of Alzheimer's disease (AD). Amyloid-[beta] peptides are produced by sequential endoproteolysis by [beta]-site amyloid-[beta] protein precursor-cleaving enzyme (BACE) followed by presenilin (PS)/[gamma]-secretase. There are several species of A[beta] due to cleavage diversity of PS/[gamma]-secretase. The predominant species in human cerebrospinal fluid (CSF) or plasma is A[beta]40, whereas A[beta]42 is much more aggregatable and accumulated in senile plaques. The level of A[beta] in the brain is determined by the balance between the generation and clearance of A[beta], including transport across the brain-blood barrier (BBB). Although the processes of A[beta] generation and degradation have been studied in some detail, knowledge of the A[beta] transport process across the BBB is limited. So far, low-density lipoprotein receptor-related protein (LRP1), P-glycoprotein (P-gp), and insulin-like growth factor-1 (IGF-1) have been identified to modify the excretion of brain A[beta] to the blood. Methods: To investigate whether macrophage colony stimulating factor (M-CSF) has a role in the A[beta] transport process, human A[beta] was injected into the lateral ventricle of the brain of M-CSF-deficient (op/op) mice. Then, plasma and brain A[beta] levels were measured by ELISA to determine the time-course of A[beta] movement from the brain to the plasma. Result: When human A[beta]40 was injected into mouse lateral ventricles, the efflux of A[beta] from the CSF to the blood was transiently decreased and delayed in M-CSF-deficient mice. Moreover, endogenous plasma A[beta]40 levels were lower in M-CSF-deficient mice. Conclusion: The results indicate that M-CSF deficiency impairs excretion of human-type A[beta]40 from the CSF to blood. We propose that M-CSF may be a novel factor that facilitates the excretion of A[beta] from the CSF to the blood via the BBB. [PUBLICATION ABSTRACT]