Title:Bone Marrow-Derived Mesenchymal Stem Cells Contribute to the Reduction of Amyloid-β Deposits and the Improvement of Synaptic Transmission in a Mouse Model of Pre-Dementia Alzheimer’s Disease
VOLUME: 10 ISSUE: 5
Author(s):Jae-sung Bae, Hee Kyung Jin, Jong Kil Lee, Jill C. Richardson and Janet E. Carter
Affiliation:Mental Health Sciences Unit, Faculty of Brain Sciences Rockefeller Building, 21 University St, University College London, WC1E 6DE, UK.
Keywords:Pre-dementia Alzheimer’s disease, bone marrow-derived mesenchymal stem cell, amyloid-β, dynamin 1, synaptic
transmission related genes.
Abstract:The remarkable potentiality of bone marrow-derived mesenchymal stem cells (BM-MSCs) after transplantation
to models of neurological disease and injury has been described. We have previously published data confirming the influence
of BM-MSCs on β-amyloid (Aβ) deposition in an Alzheimer’s disease (AD) mouse model. However, therapeutic
approaches in neurological diseases such as AD, including those for BM-MSCs, are increasingly centered on the potential
for prophylactic therapy in pro-dromal states where the underlying cause of the disease is apparent but functional deficits
are not. In order to investigate whether BM-MSCs could have a beneficial effect in high-risk pre-dementia AD individuals,
we treated young AD mice, at an age at which they display neuropathological, but not cognitive features of AD. Following
a single intra-cerebral injection of BM-MSCs, interestingly, we found a significant decrease in the cerebral Aβ
deposition compared with controls treated with PBS that was sustained up to 2 months post-injection. Expression of dynamin
1 and Synapsin 1, key pre-synaptic proteins associated with synaptic transmission, which are typically decreased in
brains of AD patients, were considerably enhanced in the brains of AD mice treated with BM-MSCs and this response
was sustained beyond 2 months. These data demonstrate that BM-MSCs produce an acute reduction in Aβ deposits and
facilitate changes in key proteins required for synaptic transmission. These findings suggest that BM-MSC transplantation
warrants further investigation as a potential therapy for early intervention in pro-dromal AD.
