The AppNL-G-F mouse retina is a site for preclinical Alzheimer’s disease diagnosis and research

Vandenabeele, Marjan; Veys, Lien; Lemmens, Sophie; Hadoux, Xavier; Gelders, Géraldine; Masin, Luca; Serneels, Lutgarde; Theunis, Jan; Saito, Takashi; Saido, Takaomi C.; Jayapala, Murali; Boever, Patrick De; Strooper, Bart De; Stalmans, Ingeborg; Wijngaarden, Peter van; Moons, Lieve; Groef, Lies De

doi:10.1101/2020.07.25.220707

Cited by 5 publications

(6 citation statements)

References 57 publications

(64 reference statements)

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“…These vascular changes may be caused by deposition of Aβ proteins [34]. Local microglial reactivity around Aβ plaques can affect retinal vein morphology and lead to a decrease in vascular density [35]. The retinal vascular and capillary networks can also provide valuable insights into the brain of AD patients [36,37].…”

Section: Discussionmentioning

confidence: 99%

Changes in retinal multilayer thickness and vascular network of patients with Alzheimer’s disease

et al. 2021

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Background Retinal biomarkers of Alzheimer’s disease (AD) have been extensively investigated in recent decades. Retinal nervous and vascular parameters can reflect brain conditions, and they can facilitate early diagnosis of AD. Objective Our study aimed to evaluate the difference in retinal neuro-layer thickness and vascular parameters of patients with AD and healthy controls (HCs). Methods Non-invasive optical coherence tomography angiography (OCTA) was used to determine the combined thickness of the retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL), as well as the full retinal thickness (FRT). The vascular branching (VB), vascular curvature (VC), and vascular density (VD) for AD and HC groups were also obtained. The Mini-Mental State Examination (MMSE) was used to evaluate the cognitive performance of all the participants. After obtaining all the parameters, two-way analysis of variance (ANOVA) was used to compare the mean values of all the retinal parameters of the patients with AD and the HCs. Pearson's correlation was used to test the association between retinal parameters, MMSE scores, and vascular parameters. Results Seventy-eight eyes from 39 participants (19 AD and 20 HC; male, 52.6% in AD and 45.0% in HC; mean [standard deviation] age of 73.79 [7.22] years in AD and 74.35 [6.07] years in HC) were included for the analysis. The average RNFL + GCL thickness (106.32 ± 7.34 μm), FRTs of the four quadrants (290.35 ± 13.05 μm of inferior quadrant, 294.68 ± 9.37 μm of superior quadrant, 302.97 ± 6.52 μm of nasal quadrant, 286.02 ± 13.74 μm of temporal quadrant), and retinal VD (0.0148 ± 0.003) of patients with AD, compared with the HCs, were significantly reduced (p < 0.05). Retinal thickness was significantly correlated with the MMSE scores (p < 0.05). Meanwhile, retinal VD was significantly correlated with the average RNFL + GCL thickness (r2 = 0.2146, p < 0.01). When the vascular parameters were considered, the sensitivity of the AD diagnosis was increased from 0.874 to 0.892. Conclusion Our study suggested that the patients with AD, compared with age-matched HCs, had significantly reduced RNFL + GCL thickness and vascular density. These reductions correlated with the cognitive performance of the participants. By combining nerve and vessel parameters, the diagnosis of AD can be improved using OCTA technology. Trail registration Name of the registry: Chinese Clinical Trail Registry, Trial registration number: ChiCTR2000035243, Date of registration: Aug. 5, 2020. URL of trial registry record: http://www.chictr.org.cn/index.aspx

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Section: Discussionmentioning

confidence: 99%

Changes in retinal multilayer thickness and vascular network of patients with Alzheimer’s disease

et al. 2021

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“…These vascular changes may be caused by the deposition of Aβ protein [29]. Local microglia reactivity around Aβ plaques could affect retinal vein morphology and lead to the decrease of vascular density [30]. The retinal vascular and even capillary network can also provide a valuable insight on AD brain [31,32].…”

Section: Discussionmentioning

confidence: 99%

Changes in Retinal Multilayer Thickness and Vascular Network of Patients With Alzheimer’s Disease

Mei

Zou

Qiu

et al. 2021

Preprint

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Background: Retinal biomarkers of Alzheimer’s disease (AD) were largely investigated during last decades. Brain conditions could be reflected by retinal nervous and vascular parameters. It can be used to enhance the accuracy of early diagnosis of AD.Objective: Our study aimed to evaluate the difference of retinal neuro-layer thickness and vascular parameters between AD patients and health control (HC) subjects.Methods: Non-invasive technology of optical coherence tomography angiography (OCTA) were adopted to acquire the combination thickness of retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL), as well as the full retinal thickness (FRT). Vascular branch (VB), vascular curvature (VC), and vascular density (VD) were also collected in AD and HC groups. Mini-mental state examination (MMSE) was adopted to evaluate the cognitive levels of all subjects. After obtaining all the parameters, we used Mann-Whitney U test to compare the mean values of all retinal regions parameters between ADs and HCs. Pearson's correlation was used to test the association between retinal parameters and MMSE score, and vascular parameters.Results: Compared with HCs, the RNFL+GCL thickness of inferior quadrant, FRT of inferior and temporal quadrant, and retinal VD of patients with AD were significantly reduced (p < 0.05). The retinal thickness had significant correlations with MMSE scores (p < 0.05). Meanwhile, the retinal VD was significantly correlated with the average RNFL+GCL thickness (p < 0.05, r = 0.5956).Conclusion: In conclusion, our study suggested that AD patients had significant reduced RNFL+GCL thickness and vascular density compared with the age-matched HCs. Meanwhile, these reductions correlated with the cognitive level of the subjects. Trial registration number: ChiCTR2000035243Date of registration: Aug., 5, 2020URL of trial registry record: http://www.chictr.org.cn/index.aspx

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“…Retinal imaging has emerged as one avenue for preclinical AD detection, as a variety of transgenic mouse models of the disease and postmortem studies of people with AD have indicated that amyloid beta and tau accumulate in the retina. 6,[35][36][37][38] In addition, neurodegeneration of the inner retina and optic nerve, as well as retinal vascular changes have been described in the disease. [39][40][41][42] Accordingly, a variety of retinal imaging biomarkers have been evaluated in AD.…”

Section: Alzheimer's Diseasementioning

confidence: 99%

“…In vitro and preclinical studies have suggested that low-order, soluble amyloid-beta oligomers cause Rayleigh scattering of light and thus a distinct reflectance pattern that can be captured with a hyperspectral camera. 38,[77][78][79] The use of retinal hyperspectral imaging for the detection of AD has been explored in three clinical studies. Overall, these have shown that retinal hyperspectral imaging can be used to differentiate people with AD from controls.…”

Section: Hyperspectral Imaging In Alzheimer's Diseasementioning

confidence: 99%

Retinal imaging biomarkers of neurodegenerative diseases

Christinaki

Kulenovic

Hadoux

et al. 2021

Clinical and Experimental Optometry

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The timely detection of neurodegenerative diseases is central to improving clinical care as well as enabling the development and deployment of disease-modifying therapies. Retinal imaging is emerging as a method to detect features of a number of neurodegenerative diseases, given the anatomical and functional similarities between the retina and the brain. This review provides an overview of the current status of retinal imaging biomarkers of neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Lewy body dementia, frontotemporal dementia, Huntington's disease and multiple sclerosis. Whilst research findings are promising, efforts to harmonise study designs and imaging methods will be important in translating these findings into clinical care. Doing so may mean that eye care providers will play important roles in the detection of a variety of neurodegenerative diseases in future.

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The App^NL-G-F mouse retina is a site for preclinical Alzheimer’s disease diagnosis and research

Cited by 5 publications

References 57 publications

Changes in retinal multilayer thickness and vascular network of patients with Alzheimer’s disease

Changes in retinal multilayer thickness and vascular network of patients with Alzheimer’s disease

Changes in Retinal Multilayer Thickness and Vascular Network of Patients With Alzheimer’s Disease

Retinal imaging biomarkers of neurodegenerative diseases

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