Transplant recipients of hematopoietic stem cells with a hereditary version of AD developed the disease at an accelerated rate.
Researchers from the University of British Colombia have discovered that familial Alzheimers disease (AD) can be transferred via bone marrow transplant. This changes the paradigm of AD being a disease exclusively produced in the brain to a more systemic disease. These findings suggest that donors of blood, tissue, organ, and stem cells should be screened for AD to prevent its inadvertent transfer during blood product transfusions and cellular therapies.
Senior author and immunologist Dr Wilfred Jefferies explained: This supports the idea that Alzheimers is a systemic disease where amyloids that are expressed outside of the brain contribute to central nervous system pathologyAs we continue to explore this mechanism, Alzheimers disease may be the tip of the iceberg and we need to have far better controls and screening of the donors used in blood, organ and tissue transplants as well as in the transfers of human derived stem cells or blood products.
The team, to test whether a peripheral source of amyloid could contribute to the development of AD in the brain, transplanted bone marrow containing stem cells from mice carrying a variant of the human amyloid precursor protein (APP) gene, a familial version of the disease. This gene, when cleaved, misfolded and aggregated, forms amyloid plaques that are a hallmark of AD. They performed transplants into two different strains of recipient mice: APP-knockout mice that lacked an APP gene altogether, and mice that carried a normal APP gene.
In this model of heritable AD, mice typically begin to develop plaques at nine to 10 months of age, and behavioural signs of cognitive decline begin to appear at 11 to 12 months of age. Notably, the transplant recipients began showing symptoms of cognitive decline much earlier: at six months post-transplant for the APP-knockout mice and at nine months for the normal mice.
First author Dr Chaahat Singh said: The fact that we could see significant behavioral differences and cognitive decline in the APP-knockouts at 6 months was surprising but also intriguing because it just showed the appearance of the disease that was being accelerated after being transferred.
Signs of cognitive decline in mice present as an absence of normal fear and a loss of short and long-term memory. Both groups of recipient mice also demonstrated molecular and cellular hallmarks of AD, including leaky blood-brain barriers and build-up of amyloid in the brain. The team concluded, after observing the transfer of disease in APP-knockout mice that lacked an APP gene altogether, that the mutated gene in the donor cells can cause the disease. They also concluded that, from observing that recipient animals that carried a normal APP gene are susceptible to the disease, this suggests that the disease can be transferred to healthy individuals.
The transplanted stem cells were hematopoietic cells so the researchers demonstration of amyloid in the brains of APP knockout mice shows definitively that AD can result from amyloid that is produced outside of the central nervous system (CNS). Furthermore, the study demonstrates that the mutated human gene can transfer the disease in a different species.
Moving forward, the scientists plan to test whether transplanting tissues from normal mice to mice with familial AD could mitigate the disease, as well as test whether the disease is transferable via other types of transplants or transfusions. Dr Jefferies commented: In this study, we examined bone marrow and stem cells transplantation. However, next it will be important to examine if inadvertent transmission of disease takes place during the application of other forms of cellular therapies, as well as to directly examine the transfer of disease from contaminated sources, independent from cellular mechanisms.
This study is published in Stem Cell Reports.
Read this article:
Hereditary Alzheimer's disease can be transferred via transplants - Drug Target Review
- Politics of Stem Cell Research - May 7th, 2011 [May 7th, 2011]
- Obama Ends Funding Ban for Stem Cell Research - May 8th, 2011 [May 8th, 2011]
- Stem Cell Research: A Father's Fight - May 10th, 2011 [May 10th, 2011]
- Human Embryonic stem cell research - May 11th, 2011 [May 11th, 2011]
- Frost Over The World - Stem Cell Research and Turkey -26 Oct - May 20th, 2011 [May 20th, 2011]
- McCain Favors Embryonic Stem Cell Research - May 20th, 2011 [May 20th, 2011]
- US divided over stem cell research reversal - 09 Mar 09 - May 21st, 2011 [May 21st, 2011]
- The Politics and Promise of Stem Cell Research - May 22nd, 2011 [May 22nd, 2011]
- Inside Story - Obama to end stem cell research ban - March 9 - Part1 - May 30th, 2011 [May 30th, 2011]
- Cardiovascular Therapies: Spotlight on Stem Cell Research - Douglas Boyd - June 3rd, 2011 [June 3rd, 2011]
- The Human Embryo and Embryonic Stem Cell Biology: Spotlight on Stem Cell Research - June 3rd, 2011 [June 3rd, 2011]
- US appeals court lifts stem cell research ban - June 7th, 2011 [June 7th, 2011]
- Trailer for Mapping Stem Cell Research: Terra Incognita - June 9th, 2011 [June 9th, 2011]
- Politics: President Obama on Stem Cell Research - June 10th, 2011 [June 10th, 2011]
- Stem Cell Research Documentary - June 11th, 2011 [June 11th, 2011]
- TEDxSingapore - Susan Lim - Hype and hope of stem cell research - June 13th, 2011 [June 13th, 2011]
- Lou Gehrig's Disease (ALS): Spotlight on Stem Cell Research - Wrapup - June 14th, 2011 [June 14th, 2011]
- The Next Frontier in Stem Cell Research - June 17th, 2011 [June 17th, 2011]
- Robert Klein: Stem Cell Research - June 22nd, 2011 [June 22nd, 2011]
- Fibrocell Stem-Cell Wrinkle Smoother Wins FDA Clearance - June 23rd, 2011 [June 23rd, 2011]
- The Politics of Stem Cell Research - June 23rd, 2011 [June 23rd, 2011]
- A Dose of Reality on Alternative Stem Cell Treatments: What you don't know can hurt you - June 28th, 2011 [June 28th, 2011]
- Governor Tim Pawlenty Discusses Stem Cell Research - June 30th, 2011 [June 30th, 2011]
- The EU and stem cell research - July 5th, 2011 [July 5th, 2011]
- Parkinson's Disease: Spotlight on Stem Cell Research - Jeff Bronstein - July 6th, 2011 [July 6th, 2011]
- Cardiovascular Therapies: Spotlight on Stem Cell Research - Yung-Wei Chi - July 7th, 2011 [July 7th, 2011]
- Spotlight on Cancer Stem Cell Research - July 11th, 2011 [July 11th, 2011]
- A Stem Cell Story - July 12th, 2011 [July 12th, 2011]
- Bishop Blair bars support for Komen breast cancer group - July 13th, 2011 [July 13th, 2011]
- Stem Cell Research In Toronto - July 14th, 2011 [July 14th, 2011]
- Arthritis: Spotlight on Stem Cell Research - Introduction - July 14th, 2011 [July 14th, 2011]
- Huntington's Disease: Spotlight on Stem Cell Research 2007 - Han Keirstead - July 15th, 2011 [July 15th, 2011]
- TMconfUK2011-08 - Stem Cell Research in the UK - Prof Charles Ffrench-Constant - July 16th, 2011 [July 16th, 2011]
- UCSF opens stem cell research building - July 16th, 2011 [July 16th, 2011]
- HIV/AIDS: Spotlight on Stem Cell Research - John Zaia - July 17th, 2011 [July 17th, 2011]
- Deafness: Spotlight on Stem Cell Research - Ebenezer Yamoah - July 22nd, 2011 [July 22nd, 2011]
- Spotlight on Basic Stem Cell Research - Irv Weissman - July 25th, 2011 [July 25th, 2011]
- Diabetes: Spotlight on Stem Cell Research - Peter Butler - July 27th, 2011 [July 27th, 2011]
- Parkinson's Disease: Spotlight on Stem Cell Research - Arnold Kriegstein - July 27th, 2011 [July 27th, 2011]
- HIV/AIDS: Spotlight on Stem Cell Research - Loren Leeds - July 27th, 2011 [July 27th, 2011]
- Alzheimer's Disease: Spotlight on Stem Cell Research - Leeza Gibbons - August 2nd, 2011 [August 2nd, 2011]
- Geron's Embryonic Stem Cell Clinical Trial for Spinal Cord Injury - August 3rd, 2011 [August 3rd, 2011]
- The Skin Gun stem cell research - August 10th, 2011 [August 10th, 2011]
- Deafness: Spotlight on Stem Cell Research - Karen Doyle - August 10th, 2011 [August 10th, 2011]
- Stem Cell Research: Huntington's Disease - August 14th, 2011 [August 14th, 2011]
- Adult and Non-Embryonic Stem Cell Research Conference at Notre Dame - August 20th, 2011 [August 20th, 2011]
- Stemcell Research and Aging - Panel 1 - August 22nd, 2011 [August 22nd, 2011]
- Texans for Stem Cell Research Learn for Life: KXAN Coverage Aired August 16th, 2011 - August 24th, 2011 [August 24th, 2011]
- Stem Cell Research: Macular Degeneration - September 18th, 2011 [September 18th, 2011]
- Brilliant Minds - Stem Cell Research | Tomorrow Today - September 25th, 2011 [September 25th, 2011]
- Ethics of Stem Cell Research (1) - September 29th, 2011 [September 29th, 2011]
- Legal and Public Policy Dimensions of Stem Cell Research - September 29th, 2011 [September 29th, 2011]
- Stem cell symposium - October 2nd, 2011 [October 2nd, 2011]
- StemCONN 2011, The Latest in Stem Cell Research - October 6th, 2011 [October 6th, 2011]
- Arthritis: Spotlight on Stem Cell Research - Mark Genovese - October 7th, 2011 [October 7th, 2011]
- Judy Roberson: Patient advocates drive stem cell scientists - October 8th, 2011 [October 8th, 2011]
- Sam Harris - Stem Cells and Morality - October 8th, 2011 [October 8th, 2011]
- Stem Cell Research, Ethics and Religion - October 9th, 2011 [October 9th, 2011]
- Stem Cells: Fulfilling the Promise - 2011 CIRM Grantee Meeting - October 10th, 2011 [October 10th, 2011]
- The Skin Gun (Stem Cell research to replace burnt off skin. Done in 3 days!) - October 13th, 2011 [October 13th, 2011]
- Alzheimer's Stem Cell Research Patient Advocate Spotlight: The Faces of Neurodegenerative Disease - Video - October 18th, 2011 [October 18th, 2011]
- Life in the Balance: Perspectives on Stem Cell Research - Video - October 18th, 2011 [October 18th, 2011]
- Stem Cell Research Funding Halt - Video - October 19th, 2011 [October 19th, 2011]
- Vatican lending hand in adult stem cell research - Video - October 20th, 2011 [October 20th, 2011]
- First Spinal-Cord Surgery With Stem Cells - Video - October 21st, 2011 [October 21st, 2011]
- Michael J. Fox Embryonic Stem Cell Research - Video - October 22nd, 2011 [October 22nd, 2011]
- stem cell research - Video - October 22nd, 2011 [October 22nd, 2011]
- Gayle Atteberry - Cloning - November 5th, 2011 [November 5th, 2011]
- It Takes Nerve: UC Irvine - Sue - November 6th, 2011 [November 6th, 2011]
- Embryonic Stem Cell Research - Video - November 9th, 2011 [November 9th, 2011]
- Adult Stem Cell Research Far Ahead of Embryonic - Video - November 10th, 2011 [November 10th, 2011]
- Is stem cell research a growing concern .flv - Video - November 10th, 2011 [November 10th, 2011]
- Forbes Discusses Stem Cell Research - Video - November 14th, 2011 [November 14th, 2011]
- Stem Cell Research Presentation - Video - November 16th, 2011 [November 16th, 2011]
- Benedict XVI: No embryonic stem cell research - Video - November 28th, 2011 [November 28th, 2011]
- Batten Disease: Spotlight on Stem Cell Research - A Father's Story - Video - November 30th, 2011 [November 30th, 2011]
- CIS 111 Digital Media Project - Stem Cell Research - Video - December 13th, 2011 [December 13th, 2011]
- Regenerative Medicine and Applications of Stem Cell Research - Video - December 20th, 2011 [December 20th, 2011]
- Stem Cell Research Today: Larry Goldstein - CIRM Science Writer's Seminar - Video - December 22nd, 2011 [December 22nd, 2011]
- CIRM Bridges Award: Building California's Stem Cell Research Workforce - Video - December 22nd, 2011 [December 22nd, 2011]