Amyloid β Protein Deposition in Osteopetrotic (op/op) Mice Is Reduced by Injections of Macrophage Colony Stimulating Factor

Abstract

The deposition of amyloid beta (Abeta) protein is a neuropathological change that characterizes Alzheimer's disease. Animals with the osteopetrosis (op/op) mutation suffer from a general skeletal sclerosis, a significantly reduced number of macrophages and osteoclasts in various tissues, and have no systemic macrophage colony stimulating factor (M-CSF). This study examined the effect that M-CSF injections had on Abeta deposition and microglial cell distribution in the brains of normal and op/op mice. Abeta-positive plaques were detected in the cerebral cortex of op/op mice, but not in normal mice. M-CSF reduced the numbers of Abeta-positive plaques in op/op mice. The microglial cell population was reduced in op/op mice compared with normal mice, and M-CSF increased the numbers to 65.8% of that observed in normal mice. Our results suggest that a clearer understanding of the role that microglial cells play in Abeta deposition may help determine the mechanisms involved in the pathogenesis of Alzheimer's disease.

Macrophage colony stimulating factor is associated with excretion of amyloid‐β peptides from cerebrospinal fluid to peripheral blood

“…There has been some controversy as to whether M‐CSF can induce deposition of Aβ in mouse brain 12–14 . To determine whether M‐CSF is associated with Aβ metabolism in the central nervous system, we investigated how exogenously injected Aβ is metabolized in M‐CSF‐deficient mice.…”

“…The following antibodies against Aβ were used. Polyclonal, forAβ40: AB5074P (anti‐34–40 of Aβ40; Chemicon, Temecula, CA, USA) 16 and FCA3340 (anti‐33–40 of Aβ40; EMD Biosciences, San Diego, CA, USA); for Aβ42: AB5078P (anti‐37–42 of Aβ42; Chemicon) 12,13 and FCA3542 (anti‐35–42 of Aβ42; EMD Biosciences); forAβ40/42: AB5076 (anti‐40/42; Chemicon); 17 for mouse Aβ: NE1012 (anti‐mouse 3–16 of Aβ40; EMD Biosciences); monoclonal, 4G8 (anti‐17–24).…”

“…There has been some controversy as to whether M-CSF can induce deposition of Ab in mouse brain. [12][13][14] To determine whether M-CSF is associated with Ab metabolism in the central nervous system, we investigated how exogenously injected Ab is metabolized in M-CSF-deficient mice. Human Ab40 (hAb), the predominant Ab species, was microinjected (1 mg in 4 mL buffer) into the lateral ventricles.…”

“…First, plasma levels of M‐CSF in the early stages of AD is lower, 10 whereas M‐CSF levels in the cerebrospinal fluid (CSF) are higher 11 . Second, although still controversial, in M‐CSF deficient ( op / op ) mice, senile plaque‐like mouse Aβ deposition has been reported 12–14 …”

“…11 Second, although still controversial, in M-CSF deficient (op/op) mice, senile plaquelike mouse Ab deposition has been reported. [12][13][14] In the present study, we used M-CSF-deficient mice to investigate whether M-CSF is associated with Ab excretion from the CSF to the blood via the BBB. We injected human Ab into the lateral ventricles of the brain and monitored Ab levels in the brain and peripheral blood.…”