CD4 + T cells contribute to neurodegeneration in Lewy body dementia

Author:

Gate David123ORCID,Tapp Emma23ORCID,Leventhal Olivia23ORCID,Shahid Marian2ORCID,Nonninger Tim J.23,Yang Andrew C.45ORCID,Strempfl Katharina678,Unger Michael S.67ORCID,Fehlmann Tobias9ORCID,Oh Hamilton23ORCID,Channappa Divya2,Henderson Victor W.2ORCID,Keller Andreas29,Aigner Ludwig67,Galasko Douglas R.10ORCID,Davis Mark M.1112ORCID,Poston Kathleen L.2ORCID,Wyss-Coray Tony235ORCID

Affiliation:

1. Department of Neurology, Northwestern University, Chicago, IL, USA.

2. Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.

3. Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA.

4. Department of Bioengineering, Stanford University, Stanford, CA, USA.

5. Chemistry, Engineering, and Medicine for Human Health (ChEM-H), Stanford University, Stanford, CA, USA.

6. Institute of Molecular Regenerative Medicine, Paracelsus Medical University, Salzburg, Austria.

7. Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University, Salzburg, Austria.

8. QPS Austria GmbH, Parkring 12, 8074 Grambach, Austria.

9. Chair for Clinical Bioinformatics, Saarland University, Saarbrucken, Germany.

10. Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA.

11. Department of Microbiology and Immunology, School of Medicine, Stanford University, Stanford, CA, USA.

12. Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA, USA.

Abstract

Autoimmunity in Lewy body dementia Lewy body dementia (LBD) is a brain disease that leads to progressive decline in thinking, movement, and independent function. It results from the build-up of microscopic deposits called Lewy bodies, which develop from the aggregation of a misfolded protein called α-synuclein. Gate et al . observed immune cells known as T cells in the brains of LBD patients (see the Perspective by Krot and Rolls). Genomics analysis revealed that T cells traffic to the LBD brain and are associated with neuronal damage. When stimulated with α-synuclein, LBD patient T cells secrete an inflammatory protein known to damage neurons. These findings suggest an unexpected detrimental role of the immune system in LBD. —SMH

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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