Plasma levels of amyloid beta and other proinflammatory mediators in patients with age-related macular degeneration.
OBJECTIVE
To investigate the plasma levels of amyloid beta (Aβ) and select inflammatory mediators in patients with various stages of AMD compared to that of age-matched controls, and discern a relationship to disease severity.


METHODS
Plasma samples were obtained from AMD subjects at various stages of disease-early (drusen only), geographic atrophy (GA), neovascular AMD (CNV)-and from controls of similar age without AMD. Samples were analyzed using a commercially available ELISA kit (sixteen cytokines) or LC/MS/MS (Aβ isotypes). Descriptive statistics were compiled on all analytes. Analysis of covariance (ANCOVA) was conducted to compare each analyte across AMD groups while adjusting for sex and age of the patients, and in comparison to the control group. Receiver operating characteristics plots were generated for the strongest predictor variables.


RESULTS
Levels of alternative spliced CC3 proteins were significantly different between controls and CNV groups (p < 0.05), with median levels almost twice higher in CNV than in controls. There was an increasing trend for plasma levels of Αβ isotypes across AMD progressive stages (p values ranged from 0.052 to 0.0012) (ANCOVA). When adjusted for multiple comparisons analysis, plasma Aβ 1-42 levels, and its ratio with Aβ 1-40 were the most significantly associated with late AMD stages. Consistently with the ANCOVA results for Αβ isotypes, the ROC curve showed a moderate prediction (AUC = - ~ 0.78) of AMD vs control using the Aβ 1-42 isotype.


CONCLUSIONS
Plasma Aβ 1-42 may have utility as a systemic biomarker for AMD.
Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, 32 Gisborne Street, East Melbourne, VIC, 3002, Australia, rh.guymer@unimelb.edu.au.
Robyn
R
Guymer
Tania
T
Cipriani
Kay D
KD
Rittenhouse
Lyndell
L
Lim
Liubov D
LD
Robman
Wenlin
W
Li
Wenlian
W
Wang
Shibing
S
Deng
Poulabi
P
Banerjee
D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000097:blood*; D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D057092:Geographic Atrophy / Q000097:blood*; D006801:Humans; D008297:Male; D010865:Pilot Projects; D015593:Retinal Drusen / Q000097:blood; D053719:Tandem Mass Spectrometry; D057135:Wet Macular Degeneration / Q000097:blood*
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D016207:Cytokines