| Abstrakt: |
Background: The retina is increasingly recognized as a promising target to identify early changes associated with Alzheimer's disease (AD) (London, Benhar, & Schwartz, 2013). Previous studies showed retinal amyloid in AD patients in‐vivo and in post‐mortem retinal tissue of AD patients (Koronyo et al., 2017; Koronyo‐Hamaoui et al., 2011). The objective of this proof‐of‐concept study is to non‐invasively visualize amyloid‐beta (Aß)‐plaques in the retina of AD patients with a multispectral scanning laser ophthalmoscope (mSLO), using curcumin as labeling fluorophore. Method: Twenty‐two subjects with early‐onset AD (age<70, MMSE>16) and four matched controls were recruited from the Amsterdam Dementia Cohort. Subjects underwent imaging with the mSLO at baseline and after curcumin intake. Blood samples were taken at different time points for curcumin bioavailability analysis. Three sub studies were performed with different curcumin supplements (Theracurmin™, Novasol™ and Longvida™) in different dosages and duration of intake. In all three cohorts mSLO imaging was performed with three excitation wavelengths (486nm (blue) and 518nm (green)) in order to separate retinal autofluorescence from curcumin fluorescence. Retinal fluorescence images were visually assessed. Result: Baseline fluorescence images showed no abnormalities in both AD‐patients and controls. Imaging using two excitation wavelengths showed no plaque‐like alterations in the retina after curcumin intake with any of the supplements. Blood analysis showed no detectable levels of free curcumin after Theracurmin or Novasol intake curcumin (results from the Longvida cohort are in preparation), however we did find curcumin conjugates with resembling binding characteristics as curcumin (den Haan, Morrema, Rozemuller, Bouwman, & Hoozemans, 2018). Conclusion: No difference in fluorescence before and after curcumin intake was observed in this cohort of early‐onset AD patients. This may be due to insufficient uptake of curcumin, a low curcumin signal to retinal fluorescence ratio and/or absence of retinal amyloid plaques. Given the discrepancies in literature (den Haan et al., 2018; Ho, Troncoso, Knox, Stark, & Eberhart, 2014; Schon et al., 2012; Williams et al., 2017) patient cohorts including both early and late onset AD as well as replication of post‐mortem studies are needed to unequivocally proof amyloid presence in AD retinas, as potential target for in‐vivo retinal imaging. [ABSTRACT FROM AUTHOR] |
