CCR1 is an early and specific marker of Alzheimer's disease.
Chemokines are a diverse group of small proteins that effect cell signaling by binding to G-protein-coupled, seven-trans-membrane receptors. Our group had found previously that the chemokine receptor CCR1 was present in neurons and dystrophic processes in a small sample of Alzheimer's disease cases. This expanded immunohistochemical study shows that the number of CCR1-positive plaque-like structures in the hippocampus and entorhinal cortex is highly correlated to dementia state as measured by the clinical dementia rating score. CCR1 immunoreactivity is found in dystrophic, neurofilament-positive, synaptophysin-negative neurites that are associated with senile plaques containing amyloid beta peptides of the 1-42 species (Abeta42). CCR1 was not, however, associated with diffuse deposits of Abeta42. There was limited expression of CCR1 in neurofibrillary tangle-bearing neuritic processes. Astrocytes and microglia were typically negative for CCR1. Human brains from age-matched, nondemented individuals rarely displayed either CCR1 or Abeta42 immunoreactivity. Seven other types of dementing neurodegenerative diseases were examined, and all failed to demonstrate CCR1 immunopositivity unless Abeta42-positive plaques were also present. Thus, neuronal CCR1 is not a generalized marker of neurodegeneration. Rather, it appears to be part of the neuroimmune response to Abeta42-positive neuritic plaques.
Halks-Miller
Meredith
M
Pharmacopathology, Berlex Biosciences, 2600 Hilltop Drive, Richmond, CA 94804, USA. meredith_halks-miller@berlex.com
Schroeder
Miriam L
ML
Haroutunian
Vahram
V
Moenning
Ursula
U
Rossi
Michael
M
Achim
Cristian
C
Purohit
Dushyant
D
Mahmoudi
Mithra
M
Horuk
Richard
R
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis*; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000473:pathology; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000378:metabolism; D058225:Plaque, Amyloid / Q000378:metabolism* / Q000473:pathology; D054389:Receptors, CCR1; D019707:Receptors, Chemokine / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D015415:Biomarkers; C515300:CCR1 protein, human; D010446:Peptide Fragments; D054389:Receptors, CCR1; D019707:Receptors, Chemokine; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)