TY - JOUR
T1 - The hunt for brain Aβ oligomers by peripherally circulating multi-functional nanoparticles
T2 - Potential therapeutic approach for Alzheimer disease
AU - Mancini, Simona
AU - Minniti, Stefania
AU - Gregori, Maria
AU - Sancini, Giulio
AU - Cagnotto, Alfredo
AU - Couraud, Pierre Olivier
AU - Ordóñez-Gutiérrez, Lara
AU - Wandosell, Francisco
AU - Salmona, Mario
AU - Re, Francesca
PY - 2016/1/1
Y1 - 2016/1/1
N2 - We previously showed the ability of liposomes bi-functionalized with phosphatidic acid and an ApoE-derived peptide (mApoE-PA-LIP) to reduce brain Aβ in transgenic Alzheimer mice. Herein we investigated the efficacy of mApoE-PA-LIP to withdraw Aβ peptide in different aggregation forms from the brain, using a transwell cellular model of the blood-brain barrier and APP/PS1 mice. The spontaneous efflux of Aβ oligomers (Aβo), but not of Aβ fibrils, from the 'brain' side of the transwell was strongly enhanced (5-fold) in presence of mApoE-PA-LIP in the 'blood' compartment. This effect is due to a withdrawal of Aβo exerted by peripheral mApoE-PA-LIP by sink effect, because, when present in the brain side, they did not act as Aβo carrier and limit the oligomer efflux. In vivo peripheral administration of mApoE-PA-LIP significantly increased the plasma Aβ level, suggesting that Aβ-binding particles exploiting the sink effect can be used as a therapeutic strategy for Alzheimer disease. From the Clinical Editor: Alzheimer disease (AD) at present is an incurable disease, which is thought to be caused by an accumulation of amyloid-β (Aβ) peptides in the brain. Many strategies in combating this disease have been focused on either the prevention or dissolving these peptides. In this article, the authors showed the ability of liposomes bi-functionalized with phosphatidic acid and with an ApoE- derived peptide to withdraw amyloid peptides from the brain. The data would help the future design of more novel treatment for Alzheimer disease.
AB - We previously showed the ability of liposomes bi-functionalized with phosphatidic acid and an ApoE-derived peptide (mApoE-PA-LIP) to reduce brain Aβ in transgenic Alzheimer mice. Herein we investigated the efficacy of mApoE-PA-LIP to withdraw Aβ peptide in different aggregation forms from the brain, using a transwell cellular model of the blood-brain barrier and APP/PS1 mice. The spontaneous efflux of Aβ oligomers (Aβo), but not of Aβ fibrils, from the 'brain' side of the transwell was strongly enhanced (5-fold) in presence of mApoE-PA-LIP in the 'blood' compartment. This effect is due to a withdrawal of Aβo exerted by peripheral mApoE-PA-LIP by sink effect, because, when present in the brain side, they did not act as Aβo carrier and limit the oligomer efflux. In vivo peripheral administration of mApoE-PA-LIP significantly increased the plasma Aβ level, suggesting that Aβ-binding particles exploiting the sink effect can be used as a therapeutic strategy for Alzheimer disease. From the Clinical Editor: Alzheimer disease (AD) at present is an incurable disease, which is thought to be caused by an accumulation of amyloid-β (Aβ) peptides in the brain. Many strategies in combating this disease have been focused on either the prevention or dissolving these peptides. In this article, the authors showed the ability of liposomes bi-functionalized with phosphatidic acid and with an ApoE- derived peptide to withdraw amyloid peptides from the brain. The data would help the future design of more novel treatment for Alzheimer disease.
KW - Alzheimer disease
KW - Liposomes
KW - Nanoparticles
KW - Sink effect
KW - β-Amyloid oligomers
UR - http://www.scopus.com/inward/record.url?scp=84957078663&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84957078663&partnerID=8YFLogxK
U2 - 10.1016/j.nano.2015.09.003
DO - 10.1016/j.nano.2015.09.003
M3 - Article
AN - SCOPUS:84957078663
VL - 12
SP - 43
EP - 52
JO - Nanomedicine: Nanotechnology, Biology, and Medicine
JF - Nanomedicine: Nanotechnology, Biology, and Medicine
SN - 1549-9634
IS - 1
ER -