Association of Preclinical Alzheimer Disease With Optical Coherence Tomographic Angiography Findings

O’Bryhim, Bliss E.; Apte, Rajendra S.; Kung, Nina; Coble, Dean W.; Stavern, Gregory P. Van

doi:10.1001/jamaophthalmol.2018.3556

Cited by 200 publications

(235 citation statements)

References 52 publications

(81 reference statements)

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“…The discovery of pathogenic Aβ deposits and early pericyte loss in retinal blood vessels of MCI and AD could shed light onto the pathophysiological mechanisms of vascular disruption, increased BRB permeability, insufficient blood supply, disrupted immune responses, and neuronal degeneration. In light of the recent advances in live imaging of retinal blood microvessels (OCT angiography) [26,42,62,82], pericyte imaging using adaptive optics [68], and retinal amyloid imaging [35,47], these results should lead to future development of noninvasive retinal vascular amyloid and pericyte imaging technologies to facilitate early screening and monitoring of AD.…”

Section: Discussionmentioning

confidence: 99%

“…Notably, the pathological hallmarks of AD-Aβ plaques and tauopathy-were further identified in the retina of AD patients, including early-stage cases [25,46,47,50]. Noninvasive high-resolution retinal imaging technologies such as fundus imaging, optical coherence tomography (OCT), as well as recently developed OCT angiography [42,62,72], retinal amyloid imaging [46][47][48], and retinal hyperspectral imaging [35,59] incentivize the use of feasible and inexpensive retinal imaging in the clinical setting to improve AD screening and monitoring.…”

Section: Introductionmentioning

confidence: 99%

“…With regard to retinal vascular changes, a wide range of abnormalities were detected in AD patients [16,19,32,33,62] including narrowed veins, reduction of blood flow, vascular attenuation, increased width variation, reduction of branching complexity and optimality, reduced arterial fractal dimensions, and increased tortuosity [1,12,32]. Moreover, recent studies using OCT and OCT angiography demonstrated that certain retinal vascular abnormalities, both in asymptomatic and clinical AD patients, predicted cognitive impairment [7,16,22].…”

Section: Introductionmentioning

confidence: 99%

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Identification of early pericyte loss and vascular amyloidosis in Alzheimer’s disease retina

et al. 2020

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Pericyte loss and deficient vascular platelet-derived growth factor receptor-β (PDGFRβ) signaling are prominent features of the blood-brain barrier breakdown described in Alzheimer's disease (AD) that can predict cognitive decline yet have never been studied in the retina. Recent reports using noninvasive retinal amyloid imaging, optical coherence tomography angiography, and histological examinations support the existence of vascular-structural abnormalities and vascular amyloid β-protein (Aβ) deposits in retinas of AD patients. However, the cellular and molecular mechanisms of such retinal vascular pathology were not previously explored. Here, by modifying a method of enzymatically clearing non-vascular retinal tissue and fluorescent immunolabeling of the isolated blood vessel network, we identified substantial pericyte loss together with significant Aβ deposition in retinal microvasculature and pericytes in AD. Evaluation of postmortem retinas from a cohort of 56 human donors revealed an early and progressive decrease in vascular PDGFRβ in mild cognitive impairment (MCI) and AD compared to cognitively normal controls. Retinal PDGFRβ loss significantly associated with increased retinal vascular Aβ 40 and Aβ 42 burden. Decreased vascular LRP-1 and early apoptosis of pericytes in AD retina were also detected. Mapping of PDGFRβ and Aβ 40 levels in pre-defined retinal subregions indicated that certain geometrical and cellular layers are more susceptible to AD pathology. Further, correlations were identified between retinal vascular abnormalities and cerebral Aβ burden, cerebral amyloid angiopathy (CAA), and clinical status. Overall, the identification of pericyte and PDGFRβ loss accompanying increased vascular amyloidosis in Alzheimer's retina implies compromised blood-retinal barrier integrity and provides new targets for AD diagnosis and therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Identification of early pericyte loss and vascular amyloidosis in Alzheimer’s disease retina

et al. 2020

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“…In a series of 14 participants with biomarkers (PET Scan and/or Aβ 42 protein) positive for AD (preclinical AD), but cognitively healthy based on neuropsychometric testing, O'Bryhim et al concluded that the FAZ was larger and the inner fovea was thinner compared to controls. 13,14…”

Section: Is Oct Angiography Useful In Neurodegenerative Diseases?mentioning

confidence: 99%

Is OCT Angiography Useful in Neurodegenerative Diseases?

Grewal¹,

Fine²,

Fekrat³

2019

Ophthalmic Surg Lasers Imaging Retina

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“…Golzan et al observed a slight GCL thinning in 28 AD dementia patients compared to 50 Aβ− controls but no differences with preclinical AD individuals [44]. O'Bryhim et al detected an increase in the foveal avascular zone area and a reduction in the inner foveal thickness in an Aβ+ group (n = 14) compared to 16 controls [45]. Recently, van de Kreeke et al did not detect differences in macular or RNFL thickness between 18 Aβ+ and 147 Aβ− healthy elderly monozygotic twins [46].…”

Section: Discussionmentioning

confidence: 99%

Association between retinal thickness and β-amyloid brain accumulation in individuals with subjective cognitive decline: Fundació ACE Healthy Brain Initiative

et al. 2020

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Background: Optical coherence tomography (OCT) of the retina is a fast and easily accessible tool for the quantification of retinal structural measurements. Multiple studies show that patients with Alzheimer's disease (AD) exhibit thinning in several retinal layers compared to age-matched controls. Subjective cognitive decline (SCD) has been proposed as a risk factor for progression to AD. There is little data about retinal changes in preclinical AD and their correlation with amyloid-β (Aβ) uptake. Aims: We investigated the association of retinal thickness quantified by OCT with Aβ accumulation and conversion to mild cognitive impairment (MCI) over 24 months in individuals with SCD. Methods: One hundred twenty-nine individuals with SCD enrolled in Fundació ACE Healthy Brain Initiative underwent comprehensive neuropsychological testing, OCT scan of the retina and florbetaben (FBB) positron emission tomography (PET) at baseline (v0) and after 24 months (v2). We assessed the association of sixteen retinal thickness measurements at baseline with FBB-PET status (+/−) and global standardize uptake value ratio (SUVR) as a continuous measure at v0 and v2 and their predictive value on clinical status change (conversion to mild cognitive impairment (MCI)) at v2.

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Association of Preclinical Alzheimer Disease With Optical Coherence Tomographic Angiography Findings

Cited by 200 publications

References 52 publications

Identification of early pericyte loss and vascular amyloidosis in Alzheimer’s disease retina

Identification of early pericyte loss and vascular amyloidosis in Alzheimer’s disease retina

Is OCT Angiography Useful in Neurodegenerative Diseases?

Association between retinal thickness and β-amyloid brain accumulation in individuals with subjective cognitive decline: Fundació ACE Healthy Brain Initiative

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