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Is retinal vasculature a biomarker in amyloid proven Alzheimer's disease?

ABSTRACT: Introduction:The retina is a potential source of noninvasive vascular biomarkers for Alzheimer's disease (AD). We assessed retinal microvasculature in well-characterized AD cases, taking ophthalmological confounders into account. Methods:We included 48 amyloid-positive AD patients and 38 amyloid-negative cognitively normal control subjects. All participants underwent ophthalmological screening to exclude interfering ocular disease. Using a multimodal approach, we measured retinal vascular parameters, choroidal thickness, macular vascular density, and foveal avascular zone size. Results:We found no disease effects on retinal vascular measures (all ?'s < |0.15|, all P > .2), adjusted for confounders. Venular tortuosity was inversely associated with Fazekas score in control subjects (? -0.56, P < .01), while vessel density in the outer ring of the macula was inversely associated with Fazekas score in AD cases (? -0.64, P < .01). Discussion:In conclusion, retinal vasculature did not discriminate patients with AD from control subjects, despite evident changes on clinical, neuroimaging, and cerebrospinal fluid biomarkers, challenging the use of retinal vasculature measurements as AD biomarker.

SUBMITTER: Haan JD

PROVIDER: S-EPMC6517376 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Is retinal vasculature a biomarker in amyloid proven Alzheimer's disease?

den Haan Jurre J van de Kreeke Jacoba A JA van Berckel Bart N BN Barkhof Frederik F Teunissen Charlotte E CE Scheltens Philip P Verbraak Frank D FD Bouwman Femke H FH

Alzheimer's & dementia (Amsterdam, Netherlands) 20190510

<h4>Introduction</h4>The retina is a potential source of noninvasive vascular biomarkers for Alzheimer's disease (AD). We assessed retinal microvasculature in well-characterized AD cases, taking ophthalmological confounders into account.<h4>Methods</h4>We included 48 amyloid-positive AD patients and 38 amyloid-negative cognitively normal control subjects. All participants underwent ophthalmological screening to exclude interfering ocular disease. Using a multimodal approach, we measured retinal ...[more]

PMID: 31193094

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Project description:Noninvasive detection of Alzheimer's disease (AD) with high specificity and sensitivity can greatly facilitate identification of at-risk populations for earlier, more effective intervention. AD patients exhibit a myriad of retinal pathologies, including hallmark amyloid β-protein (Aβ) deposits. Burden, distribution, cellular layer, and structure of retinal Aβ plaques were analyzed in flat mounts and cross sections of definite AD patients and controls (n = 37). In a proof-of-concept retinal imaging trial (n = 16), amyloid probe curcumin formulation was determined and protocol was established for retinal amyloid imaging in live patients. Histological examination uncovered classical and neuritic-like Aβ deposits with increased retinal Aβ42 plaques (4.7-fold; P = 0.0063) and neuronal loss (P = 0.0023) in AD patients versus matched controls. Retinal Aβ plaque mirrored brain pathology, especially in the primary visual cortex (P = 0.0097 to P = 0.0018; Pearson's r = 0.84-0.91). Retinal deposits often associated with blood vessels and occurred in hot spot peripheral regions of the superior quadrant and innermost retinal layers. Transmission electron microscopy revealed retinal Aβ assembled into protofibrils and fibrils. Moreover, the ability to image retinal amyloid deposits with solid-lipid curcumin and a modified scanning laser ophthalmoscope was demonstrated in live patients. A fully automated calculation of the retinal amyloid index (RAI), a quantitative measure of increased curcumin fluorescence, was constructed. Analysis of RAI scores showed a 2.1-fold increase in AD patients versus controls (P = 0.0031). The geometric distribution and increased burden of retinal amyloid pathology in AD, together with the feasibility to noninvasively detect discrete retinal amyloid deposits in living patients, may lead to a practical approach for large-scale AD diagnosis and monitoring. National Institute on Aging award (AG044897) and The Saban and The Marciano Family Foundations.

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Is retinal vasculature a biomarker in amyloid proven Alzheimer's disease?

Publications

Is retinal vasculature a biomarker in amyloid proven Alzheimer's disease?

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