Plasma fetuin-A is associated with the severity of cognitive impairment in mild-to-moderate Alzheimer's disease.
The significance of vascular risk factors in the development and progression of Alzheimer's disease (AD) is now widely recognized. Fetuin-A is an abundant plasma protein that predicts vascular risk in a variety of clinical settings. In the context of cerebral ischemia, fetuin-A appears to be anti-inflammatory. Given the apparent importance of neuroinflammation in cognitive decline, we analyzed fetuin-A concentrations and pro-inflammatory cytokine levels in a cohort of 34 patients with mild-to-moderate AD, and compared these to age-matched controls. Further, we analyzed the relationship between plasma fetuin-A concentration and a measure of cognitive impairment using multivariate regression modeling. Plasma fetuin-A concentrations were lower in the patient group (p = 0.006) compared with controls and were significantly correlated with Mini-Mental State Examination (MMSE) score (r = 0.504, p = 0.002). Fetuin-A concentration was also significantly and inversely correlated with plasma TNF-α concentration (r = -0.496, p = 0.003). The association between MMSE performance and fetuin-A was maintained even after multivariate adjustment for other risk factors including TNF-α (adjusted R² total = 0.371). Using this model, plasma fetuin-A concentration explained 21% of the variance in MMSE scores. Further studies are needed to evaluate whether fetuin-A is related to the progression and pathogenesis of AD.
Department of Clinical Biochemistry and Immunology, Royal Sussex County Hospital, Brighton, UK. edward.smith@bsuh.nhs.uk
Edward R
ER
Smith
Ramin
R
Nilforooshan
Gary
G
Weaving
Naji
N
Tabet
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications*; D001798:Blood Proteins / Q000378:metabolism*; D016009:Chi-Square Distribution; D003072:Cognition Disorders / Q000097:blood* / Q000209:etiology*; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008609:Mental Status Schedule; D009483:Neuropsychological Tests; D013223:Statistics as Topic; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D060749:alpha-2-HS-Glycoprotein
C556354:AHSG protein, human; D001798:Blood Proteins; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D060749:alpha-2-HS-Glycoprotein