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Kameran Lashkari, Francisco J Lopez, Gianna C Teague, Sanjay Kumar, Megan M McLaughlin; Are Systemic Levels of Amyloid β Altered in Patients with Geographic Atrophy?. Invest. Ophthalmol. Vis. Sci. 201657(12):.
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© ARVO (1962-2015); The Authors (2016-present)
Amyloid β (BAM) has been implicated in local inflammatory processes within the photoreceptor-RPE-choroidal complex. Local inflammation is believed to be associated with development and progression of dry age-related macular degeneration (AMD) and geographic atrophy (GA). BAM has been considered a potential interventional target in GA to reduce the inflammatory responses and to limit progression of geographic lesions. These studies were aimed at determining whether systemic levels of BAM are altered in patients with intermediate dry AMD and GA.
BAM levels in plasma samples were evaluated in an initial study (63F:31M, mean age of 77 years) and in a second confirmatory study (56F:30M, mean age of 77 years). Subjects were divided into three groups based on clinical diagnostic criteria: Controls (AREDS stage 0), intermediate dry AMD (AREDS stage III) and GA (from GSK-sponsored study NCT01342926) number of subjects for the first and second study were n = 33, 29; n = 24, 22 and n = 37, 35 for the three groups, respectively). In the first study, levels of BAM(1–40) and BAM(1–42) were measured using LuminexTM multiplex assays; whereas in the confirmatory study BAM(1–40) levels were measured using an ELISA. An analysis of covariance using age as a covariate was used to assess differences in BAM levels across the groups.
In the initial study, plasma BAM(1–40) levels were significantly (P < 0.05) elevated in subjects with GA. There was also a statistically significant linear trend across the three groups (P < 0.05). BAM(1–40) concentrations were elevated by 8% and 30% change from control in the AREDs and GA groups, respectively. The levels of BAM(1–42) were not significantly altered. Changes in BAM(1–40) levels recapitulated the changes described above when using a different set of patients and a different measuring methodology (0% and 48% change from control for the AREDs and GA groups, respectively).
BAM(1-40) levels are elevated in patients with GA and this was confirmed in two separate studies with different methodologies. BAM(1-42) levels were unaffected by stage of AMD in one of the studies. Since BAM(1-40) participates in inflammatory pathways, these data suggest that targeting BAM(1-40) may in fact reduce progression of GA. Clinical trials are currently in progress to evaluate this hypothesis.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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