Regulating microglial miR-155 transcriptional phenotype alleviates Alzheimer’s-induced retinal vasculopathy by limiting Clec7a/Galectin-3+ neurodegenerative microglia

Acta Neuropathologica Communications, Journal Year: 2022, Volume and Issue: 10(1)

Published: Sept. 8, 2022

Single cell RNA sequencing studies identified novel neurodegeneration-associated microglial (MGnD/DAM) subtypes activated around cerebral amyloid plaques. Micro-RNA (miR)-155 of the TREM2-APOE pathway was shown to be a key transcriptional regulator MGnD phenotype. Despite growing interest in studying manifestations Alzheimer's disease (AD) retina, CNS organ accessible noninvasive high-resolution imaging, date microglia have not been studied AD retina. Here, we discovered presence and increased populations Clec7a+ Galectin-3+ retinas transgenic APPSWE/PS1L166P AD-model mice. Conditionally targeting by miR-155 ablation via tamoxifen-inducible CreERT2 system mice diminished retinal while increasing homeostatic P2ry12+ microglia. Retinal were often adhering microvessels; their depletion protected inner blood-retina barrier reduced vascular amyloidosis. Microglial further limits inflammation. Mass spectrometry analysis revealed enhanced PI3K-Akt signaling predicted IL-8 Spp1 decreases with microglia-specific knockout. Overall, this study mouse Transcriptional regulation these dysfunctional mitigated inflammation vasculopathy. The protective effects should shed light on potential treatments for damage during other ocular diseases.

Language: Английский

---

Label-free hyperspectral imaging and deep-learning prediction of retinal amyloid β-protein and phosphorylated tau

PNAS Nexus, Journal Year: 2022, Volume and Issue: 1(4)

Published: Aug. 19, 2022

Alzheimer's disease (AD) is a major risk for the aging population. The pathological hallmarks of AD-an abnormal deposition amyloid β-protein (Aβ) and phosphorylated tau (pTau)-have been demonstrated in retinas AD patients, including prodromal patients with mild cognitive impairment (MCI). Aβ pathology, especially accumulation amyloidogenic 42-residue long alloform (Aβ

Language: Английский

---

Salvianolic acid B ameliorates retinal deficits in an early-stage Alzheimer’s disease mouse model through downregulating BACE1 and Aβ generation

Acta Pharmacologica Sinica, Journal Year: 2023, Volume and Issue: 44(11), P. 2151 - 2168

Published: July 7, 2023

Language: Английский

---

Macular vessel density in the superficial plexus is not a proxy of cerebrovascular damage in non-demented individuals: data from the NORFACE cohort

Alzheimer s Research & Therapy, Journal Year: 2024, Volume and Issue: 16(1)

Published: Feb. 20, 2024

Abstract Introduction Optical coherence tomography angiography (OCT-A) is a novel tool that allows the detection of retinal vascular changes. We investigated association macular vessel density (VD) in superficial plexus assessed by OCT-A with measures cerebrovascular pathology and atrophy quantified brain magnetic resonance imaging (MRI) non-demented individuals. Methods Clinical, demographical, OCT-A, MRI data from research participants were included. analyzed regional VD burden using Fazekas scale logistic regression analysis, volume white matter hyperintensities (WMH) multiple linear analysis. also explored associations hippocampal volume, ventricle Alzheimer disease cortical signature (ADCS) thickness analyses. All analyses adjusted for age, sex, syndromic diagnosis cardiovascular variables. Results The study cohort comprised 188 participants: 89 subjective cognitive decline 99 mild impairment. No significant categories (all, p > 0.111) WMH 0.051) detected. nasal quadrant was associated to ( = 0.007), but no other detected 0.05). Discussion Retinal not proxy damage individuals, while independently amyloid status.

Language: Английский

---

Retinal peri-arteriolar versus peri-venular amyloidosis, hippocampal atrophy, and cognitive impairment: exploratory trial

Acta Neuropathologica Communications, Journal Year: 2024, Volume and Issue: 12(1)

Published: June 28, 2024

The relationship between amyloidosis and vasculature in cognitive impairment Alzheimer's disease (AD) pathogenesis is increasingly acknowledged. We conducted a quantitative topographic assessment of retinal perivascular amyloid plaque (AP) distribution individuals with both normal impaired cognition. Using retrospective dataset scanning laser ophthalmoscopy fluorescence images from twenty-eight subjects varying states, we developed novel image processing method to examine peri-arteriolar peri-venular curcumin-positive AP burden. further correlated neuroimaging measures neurocognitive scores. Our study unveiled that counts surpassed throughout the entire cohort (P < 0.0001), irrespective primary, secondary, or tertiary vascular branch location, notable increase among cognitively individuals. Moreover, secondary count was elevated 0.01). Significantly, count, particularly venules, exhibited strong correlation clinical dementia rating, Montreal score, hippocampal volume, white matter hyperintensity count. In conclusion, our exploratory analysis detected greater versus marked elevation deposition regions subjects. These findings underscore potential feasibility imaging predicting decline AD progression. Larger longitudinal studies encompassing diverse populations AD-biomarker confirmation are warranted delineate temporal-spatial dynamics continuum.

Language: Английский

---

Retinal Venular Tortuosity Jointly with Retinal Amyloid Burden Correlates with Verbal Memory Loss: A Pilot Study

Cells, Journal Year: 2021, Volume and Issue: 10(11), P. 2926 - 2926

Published: Oct. 28, 2021

Retinal imaging is a non-invasive tool to study both retinal vasculature and neurodegeneration. In this exploratory curcumin-fluorescence (RFI) study, we sought determine whether vascular features combined with amyloid burden correlate the neurocognitive status.We used quantitative RFI in cohort of patients cognitive impairment automatically compute burden. blood vessels were segmented, vessel tortuosity index (VTI), inflection index, branching angle quantified. We assessed correlations between parameters, domain Z-scores using linear regression models.Thirty-four subjects enrolled twenty-nine (55% female, mean age 64 ± 6 years) included analysis. Eleven had normal cognition 18 impaired cognition. VTI was discriminated among scores. The proximal mid-periphery count venous exhibited significant differences cognitively (0.49 1.1 vs. 0.91 1.4, p = 0.006), correlated Wechsler Memory Scale-IV SF-36 mental component score (p < 0.05).This pilot showed that venular could predict verbal memory loss. Future research needed finesse clinical application imaging-based technology.

Language: Английский

---

The Value of Optical Coherence Tomography Angiography (OCT-A) in Neurological Diseases

Diagnostics, Journal Year: 2022, Volume and Issue: 12(2), P. 468 - 468

Published: Feb. 11, 2022

Optical coherence tomography angiography (OCT-A) was commercially introduced in 2014. OCT-A allows a fast, non-invasive, three-dimensional analysis of the retinal vasculature from vitreoretinal interface to choriocapillaris. The results can be evaluated separately automated or custom-defined layers. Since its introduction, has also been used patients with neurological diseases order find and characterize biomarkers. Many have manifestations, often preceding key symptoms disease. Anatomically developmentally, retina is part brain. In contrast brain, easily accessible for imaging methods; moreover, more cost-effective than brain imaging. this review, current knowledge about findings possible biomarkers summarized discussed regarding value as diagnostic tool diseases.

Language: Английский

---

A dataset of rodent cerebrovasculature from in vivo multiphoton fluorescence microscopy imaging

Scientific Data, Journal Year: 2023, Volume and Issue: 10(1)

Published: March 17, 2023

We present MiniVess, the first annotated dataset of rodent cerebrovasculature, acquired using two-photon fluorescence microscopy. MiniVess consists 70 3D image volumes with segmented ground truths. Segmentations were created traditional processing operations, a U-Net, and manual proofreading. Code for preprocessing steps U-Net are provided. Supervised machine learning methods have been widely used automated biomedical images. While much emphasis has placed on development new network architectures loss functions, there an increased need publicly available annotated, or segmented, datasets. Annotated datasets necessary during model training validation. In particular, that collected from different labs to test generalizability models. hope this will be helpful in testing reliability tools analyzing

Language: Английский

---

Clearance of interstitial fluid (ISF) and CSF (CLIC) group‐part of Vascular Professional Interest Area (PIA), updates in 2022‐2023. Cerebrovascular disease and the failure of elimination of Amyloid‐β from the brain and retina with age and Alzheimer's disease: Opportunities for therapy

Alzheimer s & Dementia, Journal Year: 2023, Volume and Issue: 20(2), P. 1421 - 1435

Published: Oct. 28, 2023

Abstract This editorial summarizes advances from the Clearance of Interstitial Fluid and Cerebrospinal (CLIC) group, within Vascular Professional Interest Area (PIA) Alzheimer's Association International Society to Advance Research Treatment (ISTAART). The overarching objectives CLIC group are to: (1) understand age‐related physiology changes that underlie impaired clearance interstitial fluid (ISF) cerebrospinal (CSF) (CLIC); (2) cellular molecular mechanisms underlying intramural periarterial drainage (IPAD) in brain; (3) establish novel diagnostic tests for disease (AD), cerebral amyloid angiopathy (CAA), retinal vasculopathy, amyloid‐related imaging abnormalities (ARIA) spontaneous iatrogenic CAA‐related inflammation (CAA‐ri), vasomotion; (4) therapies facilitate IPAD eliminate β (Aβ) aging brain retina, prevent or reduce AD CAA pathology ARIA side events associated with immunotherapy.

Language: Английский

---

Retinal organoids from human-induced pluripotent stem cells: From studying retinal dystrophies to early diagnosis of Alzheimer’s and Parkinson’s disease

Seminars in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 144, P. 77 - 86

Published: Oct. 6, 2022

Language: Английский

---