Blood cell-produced amyloid-β induces cerebral Alzheimer-type pathologies and behavioral deficits.

Molecular Psychiatry
Hao-Lun SunYan-Jiang Wang

Abstract

It is traditionally believed that cerebral amyloid-beta (Aβ) deposits are derived from the brain itself in Alzheimer's disease (AD). Peripheral cells such as blood cells also produce Aβ. The role of peripherally produced Aβ in the pathogenesis of AD remains unknown. In this study, we established a bone marrow transplantation model to investigate the contribution of blood cell-produced Aβ to AD pathogenesis. We found that bone marrow cells (BMCs) transplanted from APPswe/PS1dE9 transgenic mice into wild-type (Wt) mice at 3 months of age continuously expressed human Aβ in the blood, and caused AD phenotypes including Aβ plaques, cerebral amyloid angiopathy (CAA), tau hyperphosphorylation, neuronal degeneration, neuroinflammation, and behavioral deficits in the Wt recipient mice at 12 months after transplantation. Bone marrow reconstitution in APPswe/PS1dE9 mice with Wt-BMCs at 3 months of age reduced blood Aβ levels, and alleviated brain Aβ burden, neuronal degeneration, neuroinflammation, and behavioral deficits in the AD model mice at 12 months after transplantation. Our study demonstrated that blood cell-produced Aβ plays a significant role in AD pathogenesis, and the elimination of peripheral production of Aβ can decrease bra...Continue Reading

References

Aug 4, 1995·Biochemical and Biophysical Research Communications·M ChenH L Fernandez
Dec 6, 1994·Proceedings of the National Academy of Sciences of the United States of America·M CitronD J Selkoe
Oct 6, 2000·Amyloid : the International Journal of Experimental and Clinical Investigation : the Official Journal of the International Society of Amyloidosis·T A DaviesE R Simons
Jun 11, 2005·Journal of Thrombosis and Haemostasis : JTH·R StarkeS Machin
Jan 3, 2009·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Alex E RoherMarwan N Sabbagh
Aug 1, 2014·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Yvonne S EiseleMathias Jucker
Mar 31, 2016·EMBO Molecular Medicine·Dennis J Selkoe, John Hardy
Jul 2, 2016·Annals of Internal Medicine·Gustaf EdgrenOlof Nyrén
Sep 7, 2016·JAMA Neurology·Jinte MiddeldorpTony Wyss-Coray
Mar 30, 2017·Acta Neuropathologica·Diane L RitchieJames W Ironside
Sep 30, 2017·Nature Reviews. Neurology·Jun WangYan-Jiang Wang
Mar 7, 2018·Acta Neuropathologica Communications·Michael BurwinkelMichael Baier
Jun 6, 2018·Molecular Psychiatry·Lin-Lin ShenYan-Jiang Wang
May 1, 2019·Neuroscience Bulletin·Xian-Le BuYan-Jiang Wang
May 8, 2020·Nature·Axel MontagneBerislav V Zlokovic

❮ Previous
Next ❯

Citations

Jan 2, 2021·Frontiers in Human Neuroscience·Sidra TabassumLi Yang

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alzheimer's Disease: Amyloid Beta

Alzheimer's disease is a neurodegenerative disease associated with the accumulation of amyloid plaques in the brain; these plaques are comprised of amyloid beta deposits. Here is the latest research in this field.

Alzheimer's Disease: Animal Models

Alzheimer's disease is a neurodegenerative disease which can be studied using various experimental systems. This feed focuses on animal models used for Alzheimer's disease research.