No difference in retinal fluorescence after oral curcumin intake in amyloid‐proven AD cases compared to controls

Haan, Jurre den; Ruyter, Frederique J. Hart de; Lochocki, Benjamin; Kroon, Maurice A.G.M.; Kemper, E. Marleen; Teunissen, Charlotte E.; Berckel, Bart van; Scheltens, Philip; Hoozemans, Jeroen J.M.; Kreeke, Aleid van de; Verbraak, Frank D.; Boer, Johannes F. de; Bouwman, Femke H.

doi:10.1002/dad2.12347

Cited by 3 publications

(4 citation statements)

References 34 publications

(108 reference statements)

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“…Methodological differences in curcumin protocols and quantification may explain the varied findings (Table 1). Ngolab et al (29) theorized that the higher RAC they found compared with Koronyo et al may have been due to higher curcumin dosing over a shorter period, whereas results from den Haan et al (31) suggest that curcumin uptake may vary. In addition, the retina's inherent autofluorescence may mask the curcumin signal.…”

Section: In Vivo Detection Of Aβ Plaques In Human Retinasmentioning

confidence: 94%

“…Although the abovementioned studies strongly suggest the presence of retinal Aβ in AD and associations between retinal Aβ and cognition and/or AD pathology in the brain, den Haan et al (31) found no differences in retinal fluorescent signals between patients with biomarker positive AD and NCs using 3 formulations of oral curcumin. In participants who received the standard formulation (Longvida, Verdure Sciences, Noblesville, IN), quantitative assessment revealed no difference in hyperfluorescence between biomarker-positive AD participants and NCs.…”

Section: In Vivo Detection Of Aβ Plaques In Human Retinasmentioning

confidence: 99%

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Imaging Amyloid and Tau in the Retina: Current Research and Future Directions

Tang¹,

Blazes²,

Lee³

2023

Journal of Neuro-Ophthalmology

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Background: The retina is a key focus in the search for biomarkers of Alzheimer's disease (AD) because of its accessibility and shared development with the brain. The pathological hallmarks of AD, amyloid beta (Ab), and hyperphosphorylated tau (pTau) have been identified in the retina, although histopathologic findings have been mixed. Several imaging-based approaches have been developed to detect retinal AD pathology in vivo. Here, we review the research related to imaging AD-related pathology in the retina and implications for future biomarker research. Evidence Acquisition: Electronic searches of published literature were conducted using PubMed and Google Scholar.Results: Curcumin fluorescence and hyperspectral imaging are both promising methods for detecting retinal Ab, although both require validation in larger cohorts. Challenges remain in distinguishing curcumin-labeled Ab from background fluorescence and standardization of dosing and quantification methods. Hyperspectral imaging is limited by confounding signals from other retinal features and variability in reflectance spectra between individuals. To date, evidence of tau aggregation in the retina is limited to histopathologic studies. New avenues of research are on the horizon, including near-infrared fluorescence imaging, novel Ab labeling techniques, and small molecule retinal tau tracers. Artificial intelligence (AI) approaches, including machine learning models and deep learning-based image analysis, are active areas of investigation. Conclusions: Although the histopathological evidence seems promising, methods for imaging retinal Ab require further validation, and in vivo imaging of retinal tau remains elusive. AI approaches may hold the greatest promise for the discovery of a characteristic retinal imaging profile of AD. Elucidating the role of Ab and pTau in the retina will provide key insights into the complex processes involved in aging and in neurodegenerative disease.

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Section: In Vivo Detection Of Aβ Plaques In Human Retinasmentioning

confidence: 94%

Section: In Vivo Detection Of Aβ Plaques In Human Retinasmentioning

confidence: 99%

Imaging Amyloid and Tau in the Retina: Current Research and Future Directions

Tang¹,

Blazes²,

Lee³

2023

Journal of Neuro-Ophthalmology

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“…The cost-effective and non-invasive detection of retinal amyloid burden carries the potential for early AD identification and monitoring (2, 38–40). Thus, several retinal amyloid imaging methodologies have recently been developed (41, 42), such as scanning laser ophthalmoscopy (SLO) (17, 39, 42–46) and hyperspectral retinal imaging (13, 39–41). SLO imaging offers the opportunity to visualize and quantify not only the Aβ plaques (AP), but also the retinal arteries and veins (17, 44, 45, 47).…”

Section: Introductionmentioning

confidence: 99%

Distinctive retinal peri-arteriolar versus peri-venular amyloid plaque distribution correlates with the cognitive performance

Dumitrascu,

Doustar,

Fuchs

et al. 2024

Preprint

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Introduction: The vascular contribution to Alzheimer's disease (AD) is tightly connected to cognitive performance across the AD continuum. We topographically describe retinal perivascular amyloid plaque (AP) burden in subjects with normal or impaired cognition. Methods: Using scanning laser ophthalmoscopy, we quantified retinal peri-arteriolar and peri-venular curcumin-positive APs in the first, secondary and tertiary branches in twenty-eight subjects. Perivascular AP burden among cognitive states was correlated with neuroimaging and cognitive measures. Results: Peri-arteriolar exceeded peri-venular AP count (p<0.0001). Secondary branch AP count was significantly higher in cognitively impaired (p<0.01). Secondary small and tertiary peri-venular AP count strongly correlated with clinical dementia rating, hippocampal volumes, and white matter hyperintensity count. Discussion: Our topographic analysis indicates greater retinal amyloid accumulation in the retinal peri-arteriolar regions overall, and distal peri-venular regions in cognitively impaired individuals. Larger longitudinal studies are warranted to understand the temporal-spatial relationship between vascular dysfunction and perivascular amyloid deposition in AD.

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“…The cost-effective and non-invasive detection of retinal amyloid burden carries the potential for early AD identification and monitoring [ 2 , 38 – 40 ]. Thus, several retinal amyloid imaging methodologies have been recently developed [ 41 , 42 ], including scanning laser ophthalmoscopy (SLO) [ 17 , 39 , 42 – 46 ] and hyperspectral retinal imaging [ 13 , 39 – 41 ]. SLO fluorescence imaging following curcumin administration provides an opportunity to visualize and quantify not only the Aβ plaques (AP) but also the retinal arteries and veins [ 17 , 44 , 45 , 47 ].…”

Section: Introductionmentioning

confidence: 99%

Retinal peri-arteriolar versus peri-venular amyloidosis, hippocampal atrophy, and cognitive impairment: exploratory trial

Dumitrascu,

Doustar,

Fuchs

et al. 2024

acta neuropathol commun

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The relationship between amyloidosis and vasculature in cognitive impairment and Alzheimer’s disease (AD) pathogenesis is increasingly acknowledged. We conducted a quantitative and topographic assessment of retinal perivascular amyloid plaque (AP) distribution in individuals with both normal and impaired cognition. Using a retrospective dataset of scanning laser ophthalmoscopy fluorescence images from twenty-eight subjects with varying cognitive states, we developed a novel image processing method to examine retinal peri-arteriolar and peri-venular curcumin-positive AP burden. We further correlated retinal perivascular amyloidosis with neuroimaging measures and neurocognitive scores. Our study unveiled that peri-arteriolar AP counts surpassed peri-venular counts throughout the entire cohort (P < 0.0001), irrespective of the primary, secondary, or tertiary vascular branch location, with a notable increase among cognitively impaired individuals. Moreover, secondary branch peri-venular AP count was elevated in the cognitively impaired (P < 0.01). Significantly, peri-venular AP count, particularly in secondary and tertiary venules, exhibited a strong correlation with clinical dementia rating, Montreal cognitive assessment score, hippocampal volume, and white matter hyperintensity count. In conclusion, our exploratory analysis detected greater peri-arteriolar versus peri-venular amyloidosis and a marked elevation of amyloid deposition in secondary branch peri-venular regions among cognitively impaired subjects. These findings underscore the potential feasibility of retinal perivascular amyloid imaging in predicting cognitive decline and AD progression. Larger longitudinal studies encompassing diverse populations and AD-biomarker confirmation are warranted to delineate the temporal-spatial dynamics of retinal perivascular amyloid deposition in cognitive impairment and the AD continuum.

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No difference in retinal fluorescence after oral curcumin intake in amyloid‐proven AD cases compared to controls

Cited by 3 publications

References 34 publications

Imaging Amyloid and Tau in the Retina: Current Research and Future Directions

Imaging Amyloid and Tau in the Retina: Current Research and Future Directions

Distinctive retinal peri-arteriolar versus peri-venular amyloid plaque distribution correlates with the cognitive performance

Retinal peri-arteriolar versus peri-venular amyloidosis, hippocampal atrophy, and cognitive impairment: exploratory trial

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