Submyeloablative conditioning with busulfan permits bone marrow-derived cell accumulation in a murine model of Alzheimer's disease

Previous work has suggested that bone marrow (BM)-derived cells (BMDCs) accumulate within the CNS and could potentially associate with p-amyloid plaques in Alzheimer's disease (AD). To explore the accumulation of BMDCs in murine AD, we transplanted green fluorescent protein (GFP)-labeled BM cells into triple transgenic (3 x Tg) and wild-type (wt) mice using non-irradiative myelosuppresive conditioning with busulfan (BU). We find that BU (80 mg/kg) is sufficient to obtain adequate chimerism (>85%) in wt mice. In order to obtain appreciable non-irradiative chimerism in the 3 x Tg mice (>80%), anti-asialo ganglio-N-tetraosylceramide (alpha-ASGM-1) antibody was also used to reduce natural killer cell function and thereby abrogate the hybrid resistance of the 3 x Tg mouse strain. Using BU conditioning and alpha-ASGM-1 together, we observed sustained BM chimerism and BMDC accumulation within the CNS of the 3 x Tg and wt mice. In cortex and hippocampus, BMDC accumulation was perivascular in distribution and similar between 3 x Tg and wt mice, with no clear association between BMDCs and AD plaques. We conclude that non-irradiative BM chimerism can be achieved with BU in 3 x Tg mice, but requires alpha-ASGM-1 (or similar appropriate NK-cell depletion). Use of this chimerism protocol permits BMDCs accumulation in the CNS of mixed strain recipient mice although BMDCs appear to be largely perivascular within cortex and hippocampus. (C) 2015 Elsevier Ireland Ltd. All rights reserved.