Retinal pathological features and proteome signatures of Alzheimer’s disease

Acta Neuropathologica, Journal Year: 2023, Volume and Issue: 145(4), P. 409 - 438

Published: Feb. 11, 2023

Alzheimer's disease (AD) pathologies were discovered in the accessible neurosensory retina. However, their exact nature and topographical distribution, particularly early stages of functional impairment, how they relate to progression brain remain largely unknown. To better understand pathological features AD retina, we conducted an extensive histopathological biochemical investigation postmortem retina tissues from 86 human donors. Quantitative examination superior inferior temporal retinas mild cognitive impairment (MCI) patients compared those with normal cognition (NC) revealed significant increases amyloid β-protein (Aβ

Language: Английский

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Alzheimer's disease pathophysiology in the Retina

Progress in Retinal and Eye Research, Journal Year: 2024, Volume and Issue: 101, P. 101273 - 101273

Published: May 15, 2024

The retina is an emerging CNS target for potential noninvasive diagnosis and tracking of Alzheimer's disease (AD). Studies have identified the pathological hallmarks AD, including amyloid β-protein (Aβ) deposits abnormal tau protein isoforms, in retinas AD patients animal models. Moreover, structural functional vascular abnormalities such as reduced blood flow, Aβ deposition, blood-retinal barrier damage, along with inflammation neurodegeneration, been described mild cognitive impairment dementia. Histological, biochemical, clinical studies demonstrated that nature severity pathologies brain correspond. Proteomics analysis revealed a similar pattern dysregulated proteins biological pathways patients, enhanced inflammatory neurodegenerative processes, impaired oxidative-phosphorylation, mitochondrial dysfunction. Notably, investigational imaging technologies can now detect AD-specific deposits, well vasculopathy neurodegeneration living suggesting alterations at different stages links to pathology. Current exploratory ophthalmic modalities, optical coherence tomography (OCT), OCT-angiography, confocal scanning laser ophthalmoscopy, hyperspectral imaging, may offer promise assessment AD. However, further research needed deepen our understanding AD's impact on its progression. To advance this field, future require replication larger diverse cohorts confirmed biomarkers standardized retinal techniques. This will validate aiding early screening monitoring.

Language: Английский

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Biomarkers used in Alzheimer’s disease diagnosis, treatment, and prevention

Ageing Research Reviews, Journal Year: 2021, Volume and Issue: 74, P. 101544 - 101544

Published: Dec. 18, 2021

Language: Английский

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Ocular Neurodegenerative Diseases: Interconnection between Retina and Cortical Areas

Cells, Journal Year: 2021, Volume and Issue: 10(9), P. 2394 - 2394

Published: Sept. 12, 2021

The possible interconnection between the eye and central nervous system (CNS) has been a topic of discussion for several years just based on fact that is properly considered an extension brain. Both organs consist neurons derived from neural tube. visual process involves photoreceptors receive light stimulus external environment send it to retinal ganglionic cells (RGC), one cell types which retina composed. retina, internal membrane eye, processes stimuli in electric transfer brain, through optic nerve. Retinal chronic progressive neurodegeneration, may occur among elderly, can lead different disorders such as glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR). Mainly elderly population, but also younger people, ocular pathologies are cause irreversible blindness or impaired, reduced vision. Typical neurodegenerative diseases CSN group with common characteristics etiology not fully understood; some risk factors have identified, they enough justify all cases observed. Furthermore, studies shown present and, other hand, CNS pathologies, i.e., Alzheimer disease (AD) Parkinson (PD), causes morbidity mortality worldwide, show peculiar alterations at level. knowledge correlations could help understand mechanisms onset. Moreover, underlying these heterogeneous still debated. This review discusses illnesses, focusing relationship A better comprehension future new therapies, thus reducing avoiding loss vision improve quality life.

Language: Английский

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Retinal Vasculopathy in Alzheimer’s Disease

Frontiers in Neuroscience, Journal Year: 2021, Volume and Issue: 15

Published: Sept. 22, 2021

The retina has been increasingly investigated as a site of Alzheimer’s disease (AD) manifestation for over decade. Early reports documented degeneration retinal ganglion cells and their axonal projections. Our group provided the first evidence key pathological hallmarks AD, amyloid β-protein (Aβ) plaques including vascular Aβ deposits, in AD mild cognitively impaired (MCI) patients. Subsequent studies validated these findings further identified electroretinography vision deficits, (p)tau inflammation, intracellular accumulation, cell-subtype surrounding data suggest that brain follow similar trajectory during progression, probably due to common embryonic origin anatomical proximity. However, is only CNS organ feasible direct, repeated, non-invasive ophthalmic examination with ultra-high spatial resolution sensitivity. Neurovascular unit integrity maintaining normal function cerebral abnormalities are recognized early pivotal factors driving cognitive impairment AD. Likewise, such changes vessel density fractal dimensions, blood flow, foveal avascular zone, curvature tortuosity, arteriole-to-venule ratio were described patients early-stage cases. A rapidly growing number have suggested vasculopathy tightly associated deficits animal models. Importantly, we recently progressive deficiency platelet-derived growth factor receptor-β (PDGFRβ) expression pericyte loss amyloidosis angiopathy MCI Other utilizing optical coherence tomography (OCT), amyloid-fluorescence imaging hyperspectral made significant progress visualizing quantifying pathology through retina. With new advances OCT angiography, leakage, scanning laser microscopy, fluorescein angiography adaptive optics imaging, future focusing on pathologies could transform pre-clinical diagnosis monitoring.

Language: Английский

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Retina pathology as a target for biomarkers for Alzheimer's disease: Current status, ophthalmopathological background, challenges, and future directions

Alzheimer s & Dementia, Journal Year: 2023, Volume and Issue: 20(1), P. 728 - 740

Published: Nov. 2, 2023

Abstract There is emerging evidence that amyloid beta protein (Aβ) and tau‐related lesions in the retina are associated with Alzheimer's disease (AD). Aβ hyperphosphorylated (p)‐tau deposits have been described were small spots visualized by vivo imaging techniques as well degeneration of retina. These changes correlate brain deposition determined histological quantification, positron emission tomography (PET) or clinical diagnosis AD. However, literature not coherent on these histopathological findings. One important reason for this variability methods interpretation findings across different studies. In perspective, we indicate critical methodological deviations among groups suggest a roadmap moving forward how to harmonize (i) histopathologic examination retinal tissue; (ii) methods, devices, algorithms; (iii) inclusion/exclusion criteria studies aiming at biomarker validation.

Language: Английский

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Deep segmentation of OCTA for evaluation and association of changes of retinal microvasculature with Alzheimer’s disease and mild cognitive impairment

British Journal of Ophthalmology, Journal Year: 2023, Volume and Issue: 108(3), P. 432 - 439

Published: Jan. 3, 2023

Background Optical coherence tomography angiography (OCTA) enables fast and non-invasive high-resolution imaging of retinal microvasculature is suggested as a potential tool in the early detection microvascular changes Alzheimer’s Disease (AD). We developed standardised OCTA analysis framework compared their extracted parameters among controls AD/mild cognitive impairment (MCI) cross-section study. Methods defined geometrical at different layers foveal avascular zone (FAZ) from segmented images obtained using well-validated state-of-the-art deep learning models. studied these 158 subjects (62 healthy control, 55 AD 41 MCI) logistic regression to determine predicting status our subjects. Results In group, there was significant decrease vessel area length densities inner vascular complexes (IVC) with controls. The number bifurcations also significantly lower than that people. MCI group demonstrated area, densities, fractal dimension both superficial (SVC) IVC A larger tortuosity IVC, roundness FAZ SVC, can be observed Conclusion Our study demonstrates applicability for diagnosis MCI, provides standard future clinical service research. Biomarkers provide useful information decision-making MCI.

Language: Английский

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Retinal arterial Aβ₄₀ deposition is linked with tight junction loss and cerebral amyloid angiopathy in MCI and AD patients

Alzheimer s & Dementia, Journal Year: 2023, Volume and Issue: 19(11), P. 5185 - 5197

Published: May 11, 2023

Abstract INTRODUCTION Vascular amyloid beta (Aβ) protein deposits were detected in retinas of mild cognitively impaired (MCI) and Alzheimer's disease (AD) patients. We tested the hypothesis that retinal vascular tight junctions (TJs) compromised linked to status. METHODS TJ components Aβ expression capillaries larger blood vessels determined post mortem from 34 MCI or AD patients 27 normal controls correlated with neuropathology. RESULTS Severe decreases zonula occludens‐1 (ZO‐1) claudin‐5 correlating abundant arteriolar 40 deposition identified Retinal deficiency was closely associated cerebral angiopathy, whereas ZO‐1 defects pathology cognitive deficits. DISCUSSION uncovered deficiencies blood–retinal barrier markers for potential imaging targets screening monitoring. Intense suggests a common pathogenic mechanism failed clearance via intramural periarterial drainage.

Language: Английский

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Eye-tracking paradigms for the assessment of mild cognitive impairment: a systematic review

Frontiers in Psychology, Journal Year: 2023, Volume and Issue: 14

Published: July 20, 2023

Mild cognitive impairment (MCI), representing the ‘transitional zone’ between normal cognition and dementia, has become a novel topic in clinical research. Although early detection is crucial, it remains logistically challenging at same time. While traditional pen-and-paper tests require in-depth training to ensure standardized administration accurate interpretation of findings, significant technological advancements are leading development procedures for Alzheimer’s disease (AD) facilitating diagnostic process. Some protocols, however, show limitations that hamper their widespread adoption. Concerns about social economic implications increasing incidence AD underline need reliable, non-invasive, cost-effective, timely scoring methodologies. For instance, modern studies report oculomotor impairments among patients with MCI, who perform poorly visual paired-comparison tasks by ascribing less attentional resources stimuli. To accelerate Global Action Plan on Public Health Response Dementia 2017–2025, this work provides an overview research saccadic exploratory eye-movement deficits older adults MCI. The review protocol was drafted based Preferred Reporting Items Systematic Reviews Meta-Analyses guidelines. Electronic databases were systematically searched identify peer-reviewed articles published 2017 2022 examined processing MCI reported gaze parameters as potential biomarkers. Moreover, following contemporary trend remote healthcare technologies, we reviewed implemented non-commercial eye-tracking instrumentation order detect information population. Based gathered literature, eye-tracking-based paradigms may ameliorate screening assessments contribute detection. However, translate findings pertaining abnormal behavior into applications, imperative conduct longitudinal investigations both laboratory-based ecologically valid settings.

Language: Английский

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Enhanced activation of retinal progenitor cells by zinc silicate bioceramics for effective functional restoration in retinal degenerative diseases

View, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 29, 2025

Abstract Retinal degenerative diseases, primarily owing to the gradual loss of neuronal cells, could lead blindness. Transplantation retinal progenitor cells (RPCs), which had unique ability differentiate into offered promising therapeutic potential for these diseases. However, a critical challenge in stem cell therapy was efficient promotion directed proliferation and differentiation cells. To overcome this limitation, we formulated zinc silicate bioceramic (ZS) composite hydrogel. The experimental outcomes demonstrated that novel material possessed substantial advantages immense possibilities mimicking extracellular matrix environment, thereby effectively modulating differentiation. Notably, it enhanced RPCs neurons while suppressing glial In particular, ZS an exceptional capacity induce photoreceptor specialized type cell. It important highlight hydrogel predominantly facilitated through activation Tiam2‐Rac signaling pathway. Concurrently, stimulated via AKT ERK pathways. Zn ions promoted RPCs, synergistic effect Si contributed reducing inflammatory factor expression promoting RPCs. conclusion, meticulous modulation RPC mediated by bioceramics held promise strategies diseases neurodegenerative disorders.

Language: Английский

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