CCR6: a biomarker for Alzheimer's-like disease in a triple transgenic mouse model.
The inflammatory status of the brain in patients as well as animal models of Alzheimer's disease (AD) has been extensively studied. Accumulation of activated microglia producing tumor necrosis factor-α and monocyte chemotactic protein-1 contribute to the pathology of the disease. However, little is known about the changes in the spleen and associated peripheral immunity that might contribute to AD pathology. The goal of this study was to characterize phenotypic and functional changes in spleen, blood and brain cell populations that contribute to development of an AD-like disease in a triple transgenic (3xTg-AD) mouse model. The 3xTg-AD mice had increased percentages of brain Gr-1+ granulocytes, dendritic cells and macrophages, spleen and blood derived CD8+Ly6C+ memory T cells and CCR6+ B cells, as well as increased levels of secreted interleukin-6. Brain tissue from older 12 month old symptomatic 3xTg-AD female mice exhibited highly elevated mRNA expression of CCR6 compared to wild-type mice. Importantly, this pronounced increase in expression of CCR6 was also detected in brain and spleen tissue from pre-symptomatic 5--6 month old 3xTg-AD females and males. Our data demonstrate increased expression of CCR6 in the brain and peripheral immune organs of both pre-symptomatic and symptomatic 3xTg-AD mice, strongly suggesting an ongoing inflammatory process that precedes onset of clinical AD-like disease.
Subramanian
Sandhya
S
Neuroimmunology Research, Veterans Affairs Medical Center, Portland, OR 97239, USA.
Ayala
Patricia
P
Wadsworth
Teri L
TL
Harris
Christopher J
CJ
Vandenbark
Arthur A
AA
Quinn
Joseph F
JF
Offner
Halina
H
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001773:Blood Cells / Q000473:pathology*; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D053764:Presenilin-1 / Q000235:genetics; D054399:Receptors, CCR6 / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism / Q000473:pathology*; D016875:tau Proteins / Q000235:genetics
D016564:Amyloid beta-Protein Precursor; D015703:Antigens, CD; C106311:CCR6 protein, human; D016207:Cytokines; C508853:PSEN1 protein, human; D053764:Presenilin-1; D054399:Receptors, CCR6; D016875:tau Proteins