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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Pathological changes within the cerebral vasculature in Alzheimer’s disease: New perspectives

Brain Pathology, Journal Year: 2022, Volume and Issue: 32(6)

Published: March 14, 2022

Abstract Cerebrovascular disease underpins vascular dementia (VaD), but structural and functional changes to the cerebral vasculature contribute pathology cognitive decline in Alzheimer's (AD). In this review, we discuss contribution of amyloid angiopathy non‐amyloid small vessel AD, accompanying density, maintenance remodelling vessels (including alterations composition function cerebrovascular basement membrane). We consider how abnormalities constituent cells neurovascular unit – particularly endothelial pericytes impairment blood‐brain barrier (BBB) impact on pathogenesis AD. also are likely impair Aβ clearance both intra‐periarteriolar drainage (IPAD) transport peptides across BBB, impaired coupling reduced blood flow relation metabolic demand increase amyloidogenic processing APP production Aβ. review vasoactive properties themselves, probable bi‐directional relationship between dysfunction accumulation Lastly, recent methodological advances transcriptomics imaging that have provided novel insights into assessment retina allow vivo detection early stages

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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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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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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Assessment of Inner Blood–Retinal Barrier: Animal Models and Methods

Cells, Journal Year: 2023, Volume and Issue: 12(20), P. 2443 - 2443

Published: Oct. 12, 2023

Proper functioning of the neural retina relies on unique retinal environment regulated by blood–retinal barrier (BRB), which restricts passage solutes, fluids, and toxic substances. BRB impairment occurs in many vascular diseases breakdown significantly contributes to disease pathology. Understanding different molecular constituents signaling pathways involved development maintenance is therefore crucial developing treatment modalities. This review summarizes major inner (iBRB) formation maintenance, representative animal models eye with leakage. Studies Wnt/β-catenin are highlighted, critical for brain angiogenesis barriergenesis. Moreover, multiple vivo vitro methods detection analysis leakage described, along their advantages limitations. These pre-clinical assessing iBRB provide valuable experimental tools delineating mechanisms evaluating therapeutic drugs.

Language: Английский

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Neuron-level explainable AI for Alzheimer’s Disease assessment from fundus images

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: April 2, 2024

Abstract Alzheimer’s Disease (AD) is a progressive neurodegenerative disease and the leading cause of dementia. Early diagnosis critical for patients to benefit from potential intervention treatment. The retina has emerged as plausible diagnostic site AD detection owing its anatomical connection with brain. However, existing AI models this purpose have yet provide rational explanation behind their decisions not been able infer stage disease’s progression. Along direction, we propose novel model-agnostic explainable-AI framework, called Granu $$\underline{la}$$ la ̲ r Neuron-le $$\underline{v}$$ v el Expl $$\underline{a}$$ a iner (LAVA), an interpretation prototype that probes into intermediate layers Convolutional Neural Network (CNN) directly assess continuum retinal imaging without need longitudinal or clinical evaluations. This innovative approach aims validate vasculature biomarker modality evaluating Disease. Leveraged UK Biobank cognitive tests vascular morphological features demonstrate significant promise effectiveness LAVA in identifying stages across progression continuum.

Language: Английский

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Optical coherence tomography angiography reveals abnormal retinal vascular density and perfusion in patients with X-linked adrenoleukodystrophy: a cross-sectional study

Orphanet Journal of Rare Diseases, Journal Year: 2025, Volume and Issue: 20(1)

Published: Jan. 13, 2025

Abstract Purpose X-linked adrenoleukodystrophy (XALD) can affect the eyes. Existing therapies are hampered by early quantitative examination methods. This study used an optical coherence tomography angiography system (OCTA) to investigate retinal microvascular density and perfusion in XALD patients. Methods Fifty-two patients 47 age-matched controls were included this cross-sectional study. The divided into three groups (symptomatic, less symptomatic, controls). We compared foveal avascular zone area, vascular area at superficial complex (SVC) deep (DVC) of peripapillary macular between groups. correlated these measurements with scale scores. Results Compared controls, symptomatic group had significantly lower superior nasal sector SVC (MD − 4.940884; 95% CI 9.655061 0.226707; p = 0.036), 4.259225; 8.248627 0.269823; 0.032) 0.180304; 0.337135 0.023472; 0.018) peripheral ring quadrant SVC. group, exhibited a 5.635483; 10.450009 0.820957; 0.015) 0.063351; 0.116611 0.010091; 0.013) SVC; 4.817846; 8.924294 0.711399; 0.202707; 0.369499 0.035915; 0.011) greater 7.209401; 0.818716–13.600086; 0.021) 0.047320; 0.001685–0.092956; 0.039) inferior DVC. Among 52 patients, expanded disability status score (EDSS) was moderately negatively (p 0.001) 0.002) Conclusion Changes exist disease severity. OCTA has potential monitor progression XALD.

Language: Английский

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Determinants of approved acetylcholinesterase inhibitor response outcomes in Alzheimer’s disease: relevance for precision medicine in neurodegenerative diseases

Ageing Research Reviews, Journal Year: 2022, Volume and Issue: 84, P. 101819 - 101819

Published: Dec. 13, 2022

Language: Английский

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Choriocapillaris and Retinal Vascular Alterations in Presymptomatic Alzheimer's Disease

Investigative Ophthalmology & Visual Science, Journal Year: 2024, Volume and Issue: 65(1), P. 47 - 47

Published: Jan. 31, 2024

To compare optical coherence tomography angiography (OCTA) retina metrics between cognitively healthy subjects with pathological versus normal cerebrospinal fluid (CSF) Aβ42/tau ratios.

Language: Английский

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