Publications by authors named "Dieu‐Trang Fuchs"

Pathological tau isoforms, including hyperphosphorylated tau at serine 396 (pS396-tau) and tau oligomers (Oligo-tau), are elevated in the retinas of patients with mild cognitive impairment (MCI) due to Alzheimer's disease (AD) and AD dementia. These patients exhibit significant retinal ganglion cell (RGC) loss, however the presence of tau isoforms in RGCs and their impact on RGC integrity, particularly in early AD, have not been studied. Here, we analyzed retinal superior temporal cross-sections from 25 MCI or AD patients and 16 age- and sex-matched cognitively normal controls.

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  • Pathological tau isoforms, particularly hyperphosphorylated tau at serine 396, and tau oligomers were found in the retinas of patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD), indicating a potential link between tauopathy and retinal changes.
  • The study analyzed retinal cross-sections from 25 patients with MCI or AD and 16 cognitively normal controls, revealing a significant reduction in retinal ganglion cells (RGCs) and increased signs of cell distress in MCI and AD patients compared to controls.
  • Findings showed that higher amounts of pS396-tau in RGCs were strongly correlated with decreased RGC integrity and related to severity in cognitive decline, suggesting that retinal
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  • * Researchers analyzed retinal samples from AD patients (both mild cognitive impairment and dementia) and matched controls, finding significant increases in various tau isoforms, particularly in advanced AD cases.
  • * Strong correlations were identified between specific retinal tau isoforms and brain pathology, indicating that changes in the retina could reflect the severity of cognitive decline and neurodegeneration in AD patients.
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  • The study explores the connection between amyloidosis in retinal blood vessels and cognitive impairment, especially in Alzheimer's disease (AD), utilizing a new image processing method for analyzing retinal amyloid plaque distribution in individuals with varying cognitive abilities.
  • Results showed higher levels of amyloid plaques near retinal arteries compared to veins, with increased plaque counts linked to cognitive decline and neuroimaging metrics in cognitively impaired individuals.
  • The findings suggest that retinal imaging could serve as a predictive tool for cognitive decline and AD progression, highlighting the need for larger studies to better understand the relationship between retinal amyloid deposition and cognitive health over time.
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  • The retina is being studied as a promising, noninvasive way to diagnose and track Alzheimer's disease (AD) because it shows similar pathological features to those found in the brain, like amyloid and tau protein abnormalities.
  • Research has found that structural and functional issues in the retina, including reduced blood flow and inflammation, correlate with the severity of AD symptoms in patients.
  • Advanced imaging technologies are now capable of detecting AD-related changes in the retina, which could help in early diagnosis and monitoring of the disease, but more studies are needed with larger, diverse groups to confirm these findings and improve screening methods.
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Introduction: The vascular contribution to Alzheimer's disease (AD) is tightly connected to cognitive performance across the AD continuum. We topographically describe retinal perivascular amyloid plaque (AP) burden in subjects with normal or impaired cognition.

Methods: Using scanning laser ophthalmoscopy, we quantified retinal peri-arteriolar and peri-venular curcumin-positive APs in the first, secondary and tertiary branches in twenty-eight subjects.

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  • - This study investigates the presence of various pathological tau proteins in the retinas of individuals with early and advanced Alzheimer's disease (AD) and their connection to the severity of the disease.
  • - Researchers analyzed retinal and brain samples from 75 donors with conditions ranging from normal cognition to mild cognitive impairment (MCI) and AD, using advanced histopathology and digital profiling methods.
  • - The results showed significant increases in multiple tau isoforms in the retinas of AD and MCI patients compared to normal controls, suggesting a correlation between retinal changes and cognitive decline.
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This review examines the role of angiotensin-converting enzyme (ACE) in the context of Alzheimer's disease (AD) and its potential therapeutic value. ACE is known to degrade the neurotoxic 42-residue long alloform of amyloid β-protein (Aβ), a peptide strongly associated with AD. Previous studies in mice, demonstrated that targeted overexpression of ACE in CD115 myelomonocytic cells (ACE10 models) improved their immune responses to effectively reduce viral and bacterial infection, tumor growth, and atherosclerotic plaque.

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  • - Osteopontin (OPN) is a vital cytokine in bone marrow-derived macrophages (BMMΦ) that influences immune responses by promoting either an anti-inflammatory or pro-inflammatory state depending on its levels; glatiramer acetate (GA) boosts OPN expression to support healing.
  • - Using mass spectrometry for global proteome profiling, researchers found 631 differentially expressed proteins (DEPs) in macrophages with either OPN knockout or GA-induced OPN, many of which are linked to immune functions and include notable proteins such as UCHL1 and HMOX-1.
  • - The study revealed that UCHL1, tied to anti-inflammatory responses, is regulated by OPN in
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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 the retinal vascular tight junctions (TJs) were compromised and linked to disease status.

Methods: TJ components and Aβ expression in capillaries and larger blood vessels were determined in post mortem retinas from 34 MCI or AD patients and 27 cognitively normal controls and correlated with neuropathology.

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Alzheimer's disease (AD) pathologies were discovered in the accessible neurosensory retina. However, their exact nature and topographical distribution, particularly in the early stages of functional impairment, and how they relate to disease progression in the brain remain largely unknown. To better understand the pathological features of AD in the retina, we conducted an extensive histopathological and biochemical investigation of postmortem retina and brain tissues from 86 human donors.

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  • Alzheimer's disease (AD) poses a significant risk to older adults, characterized by the abnormal buildup of amyloid β-protein (Aβ) and phosphorylated tau (pTau) in the retinas of affected patients, including those with early signs of cognitive decline.
  • The accumulation of Aβ, particularly the 42-residue form, is an early indicator of AD, and its identification, along with tau pathology, is crucial for diagnosing the disease.
  • Researchers have developed a new, label-free hyperspectral imaging technique that uses deep learning to detect Aβ and pTau in retinal cross-sections, overcoming the challenges associated with traditional imaging methods involving contrast agents.
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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 of MGnD microglial phenotype. Despite growing interest in studying manifestations of Alzheimer's disease (AD) in the retina, a CNS organ accessible to noninvasive high-resolution imaging, to date MGnD microglia have not been studied in the AD retina.

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The ability to cross the blood-brain barrier (BBB) is critical for targeted therapy of the central nerve system (CNS). Six peptide vectors were covalently attached to a 50 kDa poly(β-l-malic acid)-trileucine polymer forming P/LLL(40%)/vector conjugates. The vectors were Angiopep-2 (AP2), B6, Miniap-4 (M4), and d-configurated peptides D1, D3, and ACI-89, with specificity for transcytosis receptors low-density lipoprotein receptor-related protein-1 (LRP-1), transferrin receptor (TfR), bee venom-derived ion channel, and Aβ/LRP-1 related transcytosis complex, respectively.

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Novel, neuroprotective uses of Copaxone (generic name: glatiramer acetate-GA) are being examined, primarily in neurological conditions involving cognitive decline. GA is a well-studied synthetic copolymer that is FDA-approved for immune-based treatment of relapsing remitting multiple sclerosis (RRMS). Clinical studies have explored the potential mechanism of action (MOA) and outcomes of GA immunization in patients.

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  • Visual impairments, such as loss of contrast sensitivity and color vision, are significant in Alzheimer's disease but not thoroughly researched; the ViS4M maze was designed to study these issues in mice.
  • The ViS4M features LED lights to create distinct color spaces and uses grayscale objects to test contrast sensitivity, allowing researchers to observe how mice navigate based on visual cues.
  • Initial findings indicate that AD mice show considerable deficits in color and contrast navigation even before memory symptoms appear, highlighting the maze's potential for assessing cognitive and visual impairments in aging and Alzheimer's models.
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The retina has been increasingly investigated as a site of Alzheimer's disease (AD) manifestation for over a decade. Early reports documented degeneration of retinal ganglion cells and their axonal projections. Our group provided the first evidence of the key pathological hallmarks of AD, amyloid β-protein (Aβ) plaques including vascular Aβ deposits, in the retina of AD and mild cognitively impaired (MCI) patients.

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  • A new maze design, called ViS4M, utilizes LED lights and dynamic objects to study color and contrast vision in mice based on their natural exploratory behavior.
  • * The study focuses on detecting visual deficits in Alzheimer's disease (AD) mice and normal aging, using different light conditions to assess their abilities.
  • * Results indicate that AD mice show significant color and contrast vision impairments, even when memory functions remain unaffected, highlighting the maze's effectiveness for evaluating vision in aging and disease.*
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Extensive effort has been made studying retinal pathology in Alzheimer's disease (AD) to improve early noninvasive diagnosis and treatment. Particularly relevant are vascular changes, which appear prominent in early brain pathogenesis and could predict cognitive decline. Recently, we identified platelet-derived growth factor receptor beta (PDGFRβ) deficiency and pericyte loss associated with vascular Aβ deposition in the neurosensory retina of mild cognitively impaired (MCI) and AD patients.

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Despite growing evidence for the characteristic signs of Alzheimer's disease (AD) in the neurosensory retina, our understanding of retina-brain relationships, especially at advanced disease stages and in response to therapy, is lacking. In transgenic models of AD (APP/PS1; ADtg mice), glatiramer acetate (GA) immunomodulation alleviates disease progression in pre- and early-symptomatic disease stages. Here, we explored the link between retinal and cerebral AD-related biomarkers, including response to GA immunization, in cohorts of old, late-stage ADtg mice.

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The neurosensory retina emerges as a prominent site of Alzheimer's disease (AD) pathology. As a CNS extension of the brain, the neuro retina is easily accessible for noninvasive, high-resolution imaging. Studies have shown that along with cognitive decline, patients with mild cognitive impairment (MCI) and AD often suffer from visual impairments, abnormal electroretinogram patterns, and circadian rhythm disturbances that can, at least in part, be attributed to retinal damage.

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Interleukin-34 (IL-34) is a recently discovered cytokine that acts as a second ligand of the colony stimulating factor 1 receptor (CSF1R) in addition to macrophage colony-stimulating factor (M-CSF). Similar to M-CSF, IL-34 also stimulates bone marrow (BM)-derived monocyte survival and differentiation into macrophages. Growing evidence suggests that peripheral BM-derived monocyte/macrophages (BMMO) play a key role in the physiological clearance of cerebral amyloid β-protein (Aβ).

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Impaired synaptic integrity and function due to accumulation of amyloid β-protein (Aβ) oligomers is thought to be a major contributor to cognitive decline in Alzheimer's disease (AD). However, the exact role of Aβ oligomers in synaptotoxicity and the ability of peripheral innate immune cells to rescue synapses remain poorly understood due to the metastable nature of oligomers. Here, we utilized photo-induced cross-linking to stabilize pure oligomers and study their effects vs.

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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.

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Targeted overexpression of angiotensin-converting enzyme (ACE), an amyloid-β protein degrading enzyme, to brain resident microglia and peripheral myelomonocytes (ACE10 model) substantially diminished Alzheimer's-like disease in double-transgenic APPSWE/PS1ΔE9 (AD+) mice. In this study, we explored the impact of selective and transient angiotensin-converting enzyme overexpression on macrophage behaviour and the relative contribution of bone marrow-derived ACE10 macrophages, but not microglia, in attenuating disease progression. To this end, two in vivo approaches were applied in AD+ mice: (i) ACE10/GFP+ bone marrow transplantation with head shielding; and (ii) adoptive transfer of CD115+-ACE10/GFP+ monocytes to the peripheral blood.

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