Genetic context modulates aging and degeneration in the murine retina DOI Creative Commons
Olivia J. Marola, Michael MacLean, Travis Cossette

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 20, 2024

Abstract Background Age is the principal risk factor for neurodegeneration in both retina and brain. The brain share many biological properties; thus, insights into retinal aging degeneration may shed light onto similar processes Genetic makeup strongly influences susceptibility to age-related disease. However, studies investigating have not sufficiently accounted genetic diversity. Therefore, examining molecular across different backgrounds will enhance our understanding of human-relevant brain—potentially improving therapeutic approaches these debilitating conditions. Methods Transcriptomics proteomics were employed elucidate signatures nine genetically diverse mouse strains (C57BL/6J, 129S1/SvlmJ, NZO/HlLtJ, WSB/EiJ, CAST/EiJ, PWK/PhK, NOD/ShiLtJ, A/J, BALB/cJ) lifespan. These data predicted human disease-relevant changes WSB NZO strains. Accordingly, B6, mice subjected vivo examinations at 4, 8, 12, and/or 18M, including: slit lamp, fundus imaging, optical coherence tomography, fluorescein angiography, pattern/full-field electroretinography. Retinal morphology, vascular structure, cell counts assessed ex . Results We identified common strains, which included genes associated with photoreceptor function immune activation. background modulated signatures. Analysis type-specific marker loss photoreceptors ganglion cells (RGCs) NZO, respectively. Fundus exams revealed retinitis pigmentosa-relevant pigmentary abnormalities retinas diabetic retinopathy (DR)-relevant cotton wool spots exudates retinas. Profound dysfunction confirmed WSB. Molecular analyses indicated photoreceptor-specific proteins prior loss, suggesting photoreceptor-intrinsic In addition, age-associated RGC dysfunction, concomitant microvascular was observed mice. Proteomic an early reduction protective antioxidant processes, underlie increased DR-relevant pathology NZO. Conclusions context a strong determinant aging, multi-omics resource can aid diseases eye Our investigations validated as improved preclinical models relevant neurodegenerative diseases.

Language: Английский

Alzheimer's disease pathophysiology in the Retina DOI Creative Commons
Bhakta Prasad Gaire,

Yosef Koronyo,

Dieu‐Trang Fuchs

et al.

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

Citations

25
Retina pathology as a target for biomarkers for Alzheimer's disease: Current status, ophthalmopathological background, challenges, and future directions DOI Creative Commons
Jessica Alber, Femke H. Bouwman, Jurre den Haan

et al.

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

Citations

28
HISTOLOGICAL EXAMINATION OF RETINAL FUNCTION AND THE EFFECTS OF CURCUMA LONGA ON MEMORY CORRECTION IN EXPERIMENTAL OLFACTORY BULBECTOMY RAT MODELS DOI Open Access

Ulduz Gashimova

Advances in Biology & Earth Sciences, Journal Year: 2024, Volume and Issue: 9(1), P. 216 - 222

Published: April 16, 2024

According to the latest literature data, histological studies of retina in animal models experimental Alzheimer's disease prove invaluable for identifying its early stages. The effects plant antioxidants rehabilitation can be determined by analysis retina. For this purpose, rats were used as research object. Experimental animals trained Morris maze form and study spatial memory. To herbal substances on memory correction curcuma was animals. Histological comparatively analyzed control, bulbectomized curcuma-treated after bulbectomy. materials obtained show that has a neuroprotective effect changes retinas bulbectomy dysfunctions accompanied deterioration visual

Language: Английский

Citations

14
Identification of retinal oligomeric, citrullinated, and other tau isoforms in early and advanced AD and relations to disease status DOI Creative Commons
Haoshen Shi, Nazanin Mirzaei,

Yosef Koronyo

et al.

Acta Neuropathologica, Journal Year: 2024, Volume and Issue: 148(1)

Published: July 9, 2024

Abstract This study investigates various pathological tau isoforms in the retina of individuals with early and advanced Alzheimer’s disease (AD), exploring their connection status. Retinal cross-sections from predefined superior-temporal inferior-temporal subregions corresponding brains neuropathologically confirmed AD patients a clinical diagnosis either mild cognitive impairment (MCI) or dementia ( n = 45) were compared retinas age- sex-matched normal cognition 30) non-AD 4). isoforms, including tangles, paired helical filament (PHF-tau), oligomeric-tau (Oligo-tau), hyperphosphorylated-tau (p-tau), citrullinated-tau (Cit-tau), stereologically analyzed by immunohistochemistry Nanostring GeoMx digital spatial profiling, correlated neuropathological outcomes. Our data indicated significant increases AD-related pretangle especially p-tau (AT8, 2.9-fold, pS396-tau, 2.6-fold), Cit-tau at arginine residue 209 (CitR -tau; 4.1-fold), Oligo-tau (T22 + , 9.2-fold), as well mature tangle forms like MC-1-positive (1.8-fold) PHF-tau (2.3-fold), to control retinas. MCI also exhibited substantial (5.2-fold), CitR -tau (3.5-fold), pS396-tau (2.2-fold). analysis elevated retinal epitopes: Ser214 Ser396 (2.6-fold), Ser404 (2.4-fold), Thr231 (1.8-fold), particularly patients. Strong associations found between versus brain pathology status: a) vs. Braak stage, neurofibrillary tangles (NFTs), CDR scores ρ 0.63–0.71), b) neuropil threads (NTs) ABC 0.69–0.71), c) NTs, NFTs, 0.67–0.74). Notably, strongly Aβ 42 arterial 40 r 0.76–0.86). Overall, this identifies quantifies diverse patients, underscoring link cognition. These findings advocate for further exploration tauopathy biomarkers facilitate detection monitoring via noninvasive imaging.

Language: Английский

Citations

10
Neuropathological hallmarks in the post-mortem retina of neurodegenerative diseases DOI Creative Commons
Frederique J. Hart de Ruyter,

Manon J. A. P. Evers,

Tjado H. J. Morrema

et al.

Acta Neuropathologica, Journal Year: 2024, Volume and Issue: 148(1)

Published: Aug. 19, 2024

The retina is increasingly recognised as a potential source of biomarkers for neurodegenerative diseases. Hallmark protein aggregates in the retinal neuronal tissue could be imaged through light non-invasively. Post-mortem studies have already shown presence specific hallmark proteins Alzheimer's disease, primary tauopathies, synucleinopathies and frontotemporal lobar degeneration. This study aims to assess proteinopathy post-mortem cohort with different diseases pathology retina. eyes were collected collaboration Netherlands Brain Bank from donors disease (n = 17), tauopathies 8), 27), degeneration mixed 11), other 6), cognitively normal controls 25). Multiple cross sections optic nerve immunostained using antibodies against pTau Ser202/Thr205 (AT8), amyloid-beta (4G8), alpha-synuclein (LB509), pTDP-43 Ser409/410 p62-lck ligand (p62) assessed inclusions. was observed diffuse signal neuropathological changes. Amyloid-beta vessel wall cytoplasmic granular deposits all groups. Alpha-synuclein Lewy neurites associated oligodendroglial inclusions multiple system atrophy. Anti-pTDP-43 generally showed typical inclusion bodies cases TDP-43 also later stages limbic-associated encephalopathy. P62 similar those seen anti-pTDP-43. Furthermore, significantly increasing Braak neurofibrillary tangles bodies, respectively. Mixed this consisted 6) high LB (> 4) low or moderate AD pathology, 1, NFT 6, Thal phase 5) combination low/moderate scores brain 4). There no advanced co-pathologies. In seven ≥ 4, retina, while tau group 11) not observed. From study, we conclude that reflects major Although levels copathology found brains most cases, primarily manifested main disease. These findings indicate appropriate imaging techniques, become highly accurate indicators diagnosing brain.

Language: Английский

Citations

9
Alzheimer's disease neuropathology and its estimation with fluid and imaging biomarkers DOI Creative Commons
Dietmar Rudolf Thal, Koen Poesen, Rik Vandenberghe

et al.

Molecular Neurodegeneration, Journal Year: 2025, Volume and Issue: 20(1)

Published: March 14, 2025

Abstract Alzheimer’s disease (AD) is neuropathologically characterized by the extracellular deposition of amyloid-β peptide (Aβ) and intraneuronal accumulation abnormal phosphorylated tau (τ)-protein (p-τ). Most frequently, these hallmark lesions are accompanied other co-pathologies in brain that may contribute to cognitive impairment, such as vascular lesions, transactive-response DNA-binding protein 43 (TDP-43), and/or α-synuclein (αSyn) aggregates. To estimate extent AD patients, several biomarkers have been developed. Specific tracers target visualize Aβ plaques, p-τ αSyn pathology or inflammation positron emission tomography. In addition imaging biomarkers, cerebrospinal fluid, blood-based biomarker assays reflecting AD-specific non-specific processes either already clinical use development. this review, we will introduce pathological brain, related discuss what respective determined at post-mortem histopathological analysis. It became evident initial stages plaque not detected with currently available biomarkers. Interestingly, precedes deposition, especially beginning when unable detect it. Later, takes lead accelerates pathology, fitting well known evolution measures over time. Some still lack clinically established today, TDP-43 cortical microinfarcts. summary, specific for AD-related pathologies allow accurate diagnosis based on pathobiological parameters. Although current excellent pathologies, they fail which analysis required. Accordingly, neuropathological studies remain essential understand development early stages. Moreover, there an urgent need co-pathologies, limbic predominant, age-related encephalopathy-related modify interacting p-τ. Novel approaches vesicle-based cryptic RNA/peptides help better future.

Language: Английский

Citations

1
OCT Imaging in Murine Models of Alzheimer’s Disease in a Systematic Review: Findings, Methodology and Future Perspectives DOI Creative Commons
Lídia Sánchez-Puebla, Inés López‐Cuenca, Elena Salobrar‐García

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(3), P. 528 - 528

Published: Feb. 27, 2024

The murine models of Alzheimer’s disease (AD) have advanced our understanding the pathophysiology. In vivo studies retina using optical coherence tomography (OCT) complemented histological methods; however, lack standardisation in OCT methodologies for AD has led to significant variations results different studies. A literature search PubMed and Scopus been performed review methods used these analyse methodological characteristics each study. addition, some recommendations are offered overcome challenges models. reveal a consensus on device use, retinal area analysed, segmentation techniques, analysis software. Although use same device, other parameters make direct comparison difficult. Standardisation criteria is crucial ensure consistent comparable results. This implies application uniform measurement protocols. Despite absence standardisation, proven valuable advancing pathophysiology AD.

Language: Английский

Citations

7
Choriocapillaris reduction accurately discriminates against early‐onset Alzheimer's disease DOI Creative Commons
William Robert Kwapong, Fei Tang, Peng Liu

et al.

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(6), P. 4185 - 4198

Published: May 15, 2024

This study addresses the urgent need for non-invasive early-onset Alzheimer's disease (EOAD) prediction. Using optical coherence tomography angiography (OCTA), we present a choriocapillaris model sensitive to EOAD, correlating with serum biomarkers.

Language: Английский

Citations

6
Standardization and clinical applications of retinal imaging biomarkers for cardiovascular disease: a Roadmap from an NHLBI workshop DOI
Emily Y. Chew, Stephen A. Burns, Alison G. Abraham

et al.

Nature Reviews Cardiology, Journal Year: 2024, Volume and Issue: 22(1), P. 47 - 63

Published: July 22, 2024

Language: Английский

Citations

5
Outer Retinal Thickness Is Associated With Cognitive Function in Normal Aging to Intermediate Age-Related Macular Degeneration DOI Creative Commons
Cynthia Owsley, Gerald McGwin, Thomas A. Swain

et al.

Investigative Ophthalmology & Visual Science, Journal Year: 2024, Volume and Issue: 65(5), P. 16 - 16

Published: May 8, 2024

Research on Alzheimer's disease (AD) and precursor states demonstrates a thinner retinal nerve fiber layer (NFL) compared to age-similar controls. Because AD age-related macular degeneration (AMD) both impact older adults share risk factors, we asked if thicknesses, including NFL, are associated with cognition in AMD.

Language: Английский

Citations

4