Cerebrospinal Fluid C-C Motif Chemokine Ligand 2 Correlates with Brain Atrophy and Cognitive Impairment in Alzheimer's Disease

Background: Chronic neuroinflammation has been implicated in Alzheimer's disease (AD) pathology. Objective: To investigate the association between cytokine and anti-amyloid-beta (A beta) autoantibody levels and the degree of brain atrophy and cognitive impairment in AD patients. Methods: Cerebrospinal fluid (CSF) levels of C-C motif chemokine ligand 2 (CCL2), C-X-C motif chemokine ligand 8, C-X-C motif chemokine ligand 10, interleukin 6, and anti-A beta autoantibody were evaluated in 69 AD patients. Serum levels of CCL2 and anti-A beta autoantibody were also examined. The degree of brain atrophy was assessed using the voxel-based specific regional analysis system for AD, which targets the volumes of interest (VOI) in medial temporal structures. Cognitive function was evaluated by neuropsychological testing, including the Mini-Mental State Examination (MMSE) and Frontal Assessment Battery (FAB). Results: CSF CCL2 levels correlated significantly with the severity (p = 0.023) and the extent (p = 0.022) of VOI atrophy, and with the extent of gray matter atrophy (p = 0.039) in AD patients. CSF anti-A beta autoantibody levels were inversely correlated with the severity of VOI atrophy (p = 0.020), the extent of VOI atrophy (p = 0.015), and the ratio of VOI/GM atrophy (r = -0.358, p = 0.004). CSF CCL2 levels were also inversely correlated with MMSE (p = 0.0497) and FAB scores (p = 0.016). Conclusions: CSF CCL2 levels are associated with the degree of medial temporal lobe and gray matter atrophy, and cognitive decline in AD.