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Hippocampal T cell infiltration promotes neuroinflammation and cognitive decline in a mouse model of tauopathy.
- Source :
-
Brain : a journal of neurology [Brain] 2017 Jan; Vol. 140 (1), pp. 184-200. Date of Electronic Publication: 2016 Nov 05. - Publication Year :
- 2017
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Abstract
- Alzheimer's disease is characterized by the combined presence of amyloid plaques and tau pathology, the latter being correlated with the progression of clinical symptoms. Neuroinflammatory changes are thought to be major contributors to Alzheimer's disease pathophysiology, even if their precise role still remains largely debated. Notably, to what extent immune responses contribute to cognitive impairments promoted by tau pathology remains poorly understood. To address this question, we took advantage of the THY-Tau22 mouse model that progressively develops hippocampal tau pathology paralleling cognitive deficits and reappraised the interrelationship between tau pathology and brain immune responses. In addition to conventional astroglial and microglial responses, we identified a CD8-positive T cell infiltration in the hippocampus of tau transgenic mice associated with an early chemokine response, notably involving CCL3. Interestingly, CD8-positive lymphocyte infiltration was also observed in the cortex of patients exhibiting frontemporal dementia with P301L tau mutation. To gain insights into the functional involvement of T cell infiltration in the pathophysiological development of tauopathy in THY-Tau22 mice, we chronically depleted T cells using anti-CD3 antibody. Such anti-CD3 treatment prevented hippocampal T cell infiltration in tau transgenic animals and reverted spatial memory deficits, in absence of tau pathology modulation. Altogether, these data support an instrumental role of hippocampal T cell infiltration in tau-driven pathophysiology and cognitive impairments in Alzheimer's disease and other tauopathies.<br /> (© The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.)
- Subjects :
- Aged
Animals
Cognitive Dysfunction therapy
Disease Models, Animal
Humans
Inflammation therapy
Mice
Mice, Inbred C57BL
Mice, Transgenic
Middle Aged
Tauopathies therapy
Antibodies therapeutic use
CD3 Complex immunology
CD4-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes immunology
Cerebral Cortex immunology
Chemokines immunology
Cognitive Dysfunction immunology
Hippocampus immunology
Inflammation immunology
Tauopathies immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2156
- Volume :
- 140
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Brain : a journal of neurology
- Publication Type :
- Academic Journal
- Accession number :
- 27818384
- Full Text :
- https://doi.org/10.1093/brain/aww270