Diffuse Signal Research Articles

Are background breast parenchymal features on preoperative breast MRI associated with disease-free survival in patients with invasive breast cancer?

To evaluate whether breast parenchymal features of the contralateral breast on preoperative MRI are associated with primary breast cancer characteristics and disease-free survival (DFS) in women with invasive breast cancer. Women with newly diagnosed invasive breast cancer who underwent preoperative breast MRI followed by surgery were retrospectively evaluated. Background parenchymal enhancement (BPE) on dynamic contrast-enhanced MRI and background diffusion signal (BDS) on diffusion-weighted MRI of the contralateral breast were qualitatively assessed using a four-category scale: minimal, mild, moderate, or marked. Primary breast cancer characteristics were compared based on the degree of BPE or BDS. Cox proportional hazards models were used to evaluate the association between MRI parenchymal features and DFS after adjusting for clinicopathologic features. A total of 515 women (mean age, 54years) were included. Of whom, 46 (8.9%) patients who developed disease recurrence at a median follow-up of 60months were observed. A high level (moderate/marked) of BPE or BDS was associated with younger age (≤ 45) and premenopausal status (all P < 0.05) compared to a low level (minimal/mild), but it was not associated with primary cancer characteristics such as tumor stage, grade, or subtype. Multivariable Cox proportional hazards analysis demonstrated that larger tumor size (> 2cm) (hazard ratio [HR], 3.877; P < . 001), triple-negative subtype (HR, 2.440; P = .013), and axillary node metastasis (HR, 1.823; P = .049) were associated with worse DFS. No associations were observed between background parenchymal features and disease outcomes. MRI parenchymal features, including BPE and BDS, of the contralateral breast showed no associations with primary breast cancer characteristics or DFS in women with invasive breast cancer.

Light‐Based Juxtacrine Signaling Between Synthetic Cells

Cell signaling through direct physical cell–cell contacts plays vital roles in biology during development, angiogenesis, and immune response. Intercellular communication mechanisms between synthetic cells constructed from the bottom up are majorly reliant on diffusible chemical signals, thus limiting the range of responses in receiver cells. Engineering contact‐dependent signaling between synthetic cells promises to unlock more complicated signaling schemes with spatial responses. Herein, a light‐activated contact‐dependent communication scheme for synthetic cells is designed and demonstrated. A split luminescent protein is utilized to limit signal generation exclusively to contact interfaces of synthetic cells, driving the recruitment of a photoswitchable protein in receiver cells, akin to juxtacrine signaling in living cells. The modular design not only demonstrates contact‐dependent communication between synthetic cells but also provides a platform for engineering orthogonal contact‐dependent signaling mechanisms.

Neonatal Brain MRI: Periventricular Germinal Matrix Mimicking Hypoxic-ischemic White Matter Injuries.

As pregnancy progresses, the germinal matrix volume decreases. Residual periventricular germinal matrix may be mistaken for hypoxic-ischemic white matter injury. This study aims to determine the prevalence and imaging characteristics of these findings. This retrospective study analyzed brain MRIs of newborns from 2012-2023, performed within the first week of life. MRIs were done for suspected hypoxic-ischemic injuries, post-natal neurological symptoms, and evaluation of prenatally diagnosed structural anomalies. Image analysis targeted the remnants of the frontal periventricular germinal matrix, assessing its imaging characteristics, including diffusion, T1, and T2 signal characteristics, and laterality. Frontal migrating cell bands were also assessed. Seventy newborns were included (mean gestational age at delivery was 38.3 ± 2.1 weeks, mean scan age 5.1 ± 1.9 days). Frontal periventricular gray matter was detected in 39 newborns (90% bilateral) on T2-weighted images, negatively correlated with gestational age (r = -0.31, p = 0.013); none showed decreased ADC or shortened T1 signal compared with the basal ganglia. Frontal periventricular bands were found in 37 newborns (97.3% bilateral), strongly correlating with periventricular gray matter (r = 0.71, p < 0.001). No correlation was found between clinical hypoxic-ischemic injuries and these features. The presence of frontal periventricular gray matter observed in early neonatal MRIs, without decreased ADC values or shortened T1 signal, is developmental, reflecting a late maturation phase. Careful interpretation of MRI characteristics, including diffusion, T1, and T2 signal intensities, is necessary before attributing these findings to hypoxic-ischemic white matter injury.

Multiple status signals in multinational teams: Implications of lingua franca proficiency and task expertise for informal leadership

Lingua franca proficiency and task expertise coexist in multinational teams as prominent status signals that are often relied upon to infer a member’s competence. These personal attributes, however, do not always suggest consistent information since those with lower lingua franca proficiency might be more expert at the task and vice versa. In examining their joint implications, we draw on status characteristics and expectation states theories to identify the signaling nature of each attribute. Unlike the categorically specific quality of task expertise, lingua franca proficiency possesses characteristics commensurate with both specific and diffuse signals: it represents a social group and, at the same time, carries valid information about performance for certain tasks. Using archival (Study 1) and experimental (Study 2) data, we explore how the hybrid nature of lingua franca proficiency shapes its interaction with task expertise and implications for subsequent leadership outcomes. We provide further evidence for the generalizability of our findings through a supplemental study that includes 18 interviews with current members of multinational teams across various organizations.

Characterizing the diffuse continuum excitations in the classical spin liquid h−YMnO3

We extend previous inelastic neutron scattering results on the geometrically frustrated antiferromagnet hexagonal-YMnO3, which has been suggested to belong to the class of classical spin liquids. We expand the energy transfer range of the diffuse signal up to 6.9 meV within a wide temperature range around the ordering temperature, TN. The two distinct diffuse signals in the a−b plane, the signal localized at Γ′ and the scattering intensity connecting Γ′ points over the M′, are shown to be only weakly energy dependent. In addition, an external magnetic field of up to 10.5 T applied along c is shown to have no effect on the diffuse signal. In the orthogonal scattering plane, the signals are shown to be dependent on l only through the magnetic form factor, showing that the correlations are purely two-dimensional, and supporting the origin of this to be the frustrated Mn3+ triangles. This result is corroborated by atomistic spin dynamics simulations showing similar scattering vector and temperature behaviors. Lastly, data for the spin wave scattering in the (h,0,l) plane allow for a discussion of the magnetic ground state where better agreement is found between the data and an ordered structure of the Γ1 or Γ3 symmetry, albeit crystal electric field arguments dismiss the Γ1 as a possibility. Published by the American Physical Society 2024

How the heterogeneity of the severely injured brain affects hybrid diffuse optical signals: case examples and guidelines.

A shortcoming of the routine clinical use of diffuse optics (DO) in the injured head has been that the results from commercial near-infrared spectroscopy-based devices are not reproducible, often give physiologically invalid values, and differ among systems. Besides the limitations due to the physics of continuous-wave light sources, one culprit is the head heterogeneity and the underlying morphological and functional abnormalities of the probed tissue. The aim is to investigate the effect that different tissue alterations in the damaged head have on DO signals and provide guidelines to avoid data misinterpretation. DO measurements and computed tomography scans were acquired on brain-injured patients. The relationship between the signals and the underlying tissue types was classified on a case-by-case basis. Examples and suggestions to establish quality control routines were provided. The findings suggested guidelines for carrying out DO measurements and speculations toward improved devices. We advocate for the standardization of the DO measurements to secure a role for DO in neurocritical care. We suggest that blind measurements are unacceptably problematic due to confounding effects and care using a priori and a posteriori quality control routines that go beyond an assessment of the signal-to-noise ratio that is typically utilized.

Short-range C-signaling restricts cheating behavior during Myxococcus xanthus development.

Bacteria communicate using both long- and short-range signals. Signaling affects community composition, structure, and function. Adherent communities called biofilms impact medicine, agriculture, industry, and the environment. To facilitate the manipulation of biofilms for societal benefits, a better understanding of short-range signaling is necessary. We investigated the susceptibility of short-range C-signaling to cheating during Myxococcus xanthus biofilm development. A mutant deficient in C-signaling fails to form mounds containing spores (i.e., fruiting bodies) but cheats on C-signaling by wild type in starved cell mixtures and forms spores disproportionately. We found that cheating requires sufficient wild-type cells in the initial mix and can occur both before mound formation and later during the sporulation stage of development. By restricting cheating behavior, short-range C-signaling may have been favored evolutionarily rather than long-range diffusible signaling. Cheating restrictions imposed by short-range signaling may have likewise driven the evolution of multicellularity broadly.

Molecular Mechanisms of Biofilm Formation in Helicobacter pylori.

Biofilm formation in Helicobacter pylori (H. pylori) helps bacteria survive antibiotic exposure and supports bacterial colonization and persistence in the stomach. Most of the published articles have focused on one aspect of the biofilm. Therefore, we conducted the current study to better understand the mechanism of biofilm formation, how the biofilm contributes to antibiotic resistance, and how the biofilm modifies the medication delivery mechanism. We conducted a literature review analysis of the published articles on the Helicobacter pylori biofilm between 1998 and 2024 from the PubMed database to retrieve eligible articles. After applying the inclusion and exclusion criteria, two hundred and seventy-three articles were eligible for our study. The results showed that biofilm formation starts as adhesion and progresses through micro-colonies, maturation, and dispersion in a planktonic form. Moreover, specific genes modulate each phase of biofilm formation. Few studies have shown that mechanisms, such as quorum sensing and diffusible signal factors, enhance coordination among bacteria when switching from biofilm to planktonic states. Different protein expressions were also observed between planktonic and biofilm strains, and the biofilm architecture was supported by exopolysaccharides, extracellular DNA, and outer membrane vesicles. This infrastructure is responsible for the increased survival of bacteria, especially in harsh environments or in the presence of antibiotics. Therefore, understanding the biofilm formation for H. pylori is crucial. This study illustrates biofilm formation in H. pylori to help improve the treatment of H. pylori infection.

Features of High-Precision Photothermal Analysis of Liquid Systems by Dual-Beam Thermal Lens Spectrometry.

Thermal lens spectrometry is a high-sensitivity method for measuring the optical and thermal parameters of samples of different nature. To obtain both thermal diffusivity and absorbance-based signal measurements with high accuracy and precision, it is necessary to pay attention to the factors that influence the trueness of photothermal measurements. In this study, the features of liquid objects are studied, and the influence of optical and thermal effects accompanying photothermal phenomena are investigated. Thermal lens analysis of dispersed solutions and systems with photoinduced activity is associated with a large number of side effects, the impact of which on trueness is not always possible to determine. It is necessary to take into account the physicochemical properties and optical and morphological features of the nanophase and components exhibiting photoinduced activity. The results obtained make it possible to reduce systematic and random errors in determining the thermal-diffusivity-based and absorbance-based photothermal signals for liquid objects, and also contribute to a deeper understanding of the physicochemical processes in the sample.

Prospects for γ-ray observations of the Perseus galaxy cluster with the Cherenkov Telescope Array

Galaxy clusters are expected to be both dark matter (DM) reservoirs and storage rooms for the cosmic-ray protons (CRp) that accumulate along the cluster's formation history. Accordingly, they are excellent targets to search for signals of DM annihilation and decay at γ-ray energies and are predicted to be sources of large-scale γ-ray emission due to hadronic interactions in the intracluster medium (ICM).In this paper, we estimate the sensitivity of the Cherenkov Telescope Array (CTA) to detect diffuse γ-ray emission from the Perseus galaxy cluster.We first perform a detailed spatial and spectral modelling of the expected signal for both the DM and the CRp components. For each case, we compute the expected CTA sensitivity accounting for the CTA instrument response functions. The CTA observing strategy of the Perseus cluster is also discussed.In the absence of a diffuse signal (non-detection), CTA should constrain the CRp to thermal energy ratio X 500 within the characteristic radius R 500 down to about X 500 < 3 × 10-3, for a spatial CRp distribution that follows the thermal gas and a CRp spectral index αCRp = 2.3. Under the optimistic assumption of a pure hadronic origin of the Perseus radio mini-halo and depending on the assumed magnetic field profile, CTA should measure αCRp down to about ΔαCRp ≃ 0.1 and the CRp spatial distribution with 10% precision, respectively. Regarding DM, CTA should improve the current ground-based γ-ray DM limits from clusters observations on the velocity-averaged annihilation cross-section by a factor of up to ∼ 5, depending on the modelling of DM halo substructure. In the case of decay of DM particles, CTA will explore a new region of the parameter space, reaching models with τ χ > 1027 s for DM masses above 1 TeV.These constraints will provide unprecedented sensitivity to the physics of both CRp acceleration and transport at cluster scale and to TeV DM particle models, especially in the decay scenario.

Reconstruction of intra- and extra-neurite conductivity tensors via conductivity at Larmor frequency and DWI data patterns.

The developed magnetic resonance electrical properties tomography (MREPT) techniques visualize the internal conductivity distribution at Larmor frequency by measuring the B1 transceive phase data. In biological tissues, electrical conductivity is influenced by ion concentrations and mobility. To visualize the anisotropic conductivity tensor of biological tissues, we use the Einstein-Smoluchowski equation, which links the diffusion coefficient to particle mobility. By assuming a correlation between ion mobility and water diffusivity, we aim to decompose the internal isotropic conductivity at Larmor frequency into anisotropic conductivity tensors within the intra- and extra-neurite compartments. The multi-compartment spherical mean technique (MC-SMT), utilizing both high and low b-value diffusion-weighted imaging (DWI) data, characterizes the diffusion of water molecules within and across the intra- and extra-neurite compartments by analyzing the microstructural intricacies and the foundational architectural arrangement of the brain's tissues. By analyzing the relationships between the measured DWI data, the microscopic diffusion signal, and the fiber orientation distribution function, we predict the DWI data for the intra- and extra-neurite compartments using spherical harmonic decomposition. Using the predicted DWI data for the intra- and extra-neurite compartments, we develop a conductivity tensor imaging method that operates specifically within the separated compartments. Human brain experiments, involving four healthy volunteers and a brain tumor patient, were performed to assess and confirm the reliability of the proposed method.

Interference mitigation using optimised angle diversity receiver in LiFi cellular network

Light-fidelity (LiFi) is an emerging technology for high-speed short-range mobile communications. Inter-cell interference (ICI) is an important issue that limits the system performance in an optical attocell network. Angle diversity receivers (ADRs) have been proposed to mitigate ICI. In this paper, the structure of pyramid receivers (PRs) and truncated pyramid receivers (TPRs) are studied. The coverage problems of PRs and TPRs are defined and investigated, and the lower bound of field of view (FOV) for each PD is given analytically. It is shown that the lower bound of FOV for TPR and PR are 20° and 30°, respectively. The impact of random device orientation and diffuse link signal propagation are taken into consideration. The performances of PRs and TPRs are compared, and optimised ADR structures are proposed by jointly considering the impact of tilt angle, FOV, and the number of PDs. For a transmitter-bandwidth limited system, the optimal PD values are 6 for PR and 9 for TPR, whereas, for a receiver-bandwidth limited system, the optimal PD value is 15. In addition, the double source (DS) cell system, where each LiFi AP consists of two sources transmitting the same information signals but with opposite polarity, is proved to outperform the single source cell (SS) system in interference limited or noise-plus-interference limited scenario. However, the SS cell system outperforms the DS cell system in a noise-limited scenario.

Revealing synergistic mechanisms of biochar-assisted microbial electrolysis cells in enhancing the anaerobic digestion performance of waste activated sludge: Extracellular polymeric substances characterization, enzyme activity assay, and multi-omics analysis

Although biochar (BC)-assisted microbial electrolysis cells (MEC) has been shown to improve anaerobic digestion (AD) performance of waste activated sludge (WAS), the underlying mechanisms remain unclear. This study conducted an in-depth investigation into the mechanism based on analyses of extracellular polymeric substances (EPS) characteristics, enzyme activities and multi-omics. The results showed that compared with the control group, methane production improved by 16.73 %, 21.32 %, and 29.37 % in the BC, MEC, and BC-assisted MEC (BC-MEC) groups, respectively. The reconfiguration of the protein secondary structure increased the hydrophobicity of the EPS, thereby promoting microbial aggregation. In addition, partial least-squares path modeling (PLS-PM) and mantel test based on the enzyme activity and multi-omics analyses revealed that the promotional effect of MEC on the hydrolysis of WAS was superior to that of BC, while BC was more advantageous in promoting electron transfer and biofilm formation regulated by quorum sensing. The synergistic effects of BC and MEC were exemplified in the BC-MEC group. g_norank_Aminicenantales responsible for the hydrolysis of WAS was enriched (29.6 %), and the activities of hydrolytic enzymes including α-glucosidases and proteases were increased by 29.1 % and 43.6 %, respectively. Further, the expressions of genes related to acyl homoserine lactones (AHLs) and diffusible signal factor (DSF) in quorum sensing systems, as well as the genes related to hydrogenase involved in electron transfer (mbhJKL, hyfB-JR, hypA-F, and hoxFHUY), were up-regulated in the BC-MEC group. This facilitated electron transfer and microbial communication, consequently enhancing methane production. This research significantly advances the understanding of the mechanism by which BC-assisted MEC enhances AD performance and provides valuable insights into strategies for improving energy recovery from WAS.

Bacterial communication intelligently regulates their interactions in anammox consortia under decreasing temperatures

Bacterial communication could affect their interactions, but whether this regulation has “intelligence” is still unknown. Here, we operated an anammox reactor under temperature gradient from 35 °C to 15 °C. As results, expression abundance of bacterial communication genes increased by 12 % significantly after temperature declined. Division of labor among distinct signal molecules was evidenced by complementary roles of acyl-homoserine lactones (AHLs) and diffusible signal factor (DSF) in affecting bacterial interactions and niche differentiation respectively. DSF based inter-and intra-communication helped bacteria match their investments and rewards during cross-feedings. When temperature was below 25 °C, transcription regulator Clp governed by DSF inclined to promote folate and molybdenum cofactor biosynthesis, which coincidentally benefited one anammox species more than another. Meanwhile, for the anammox species with lower benefits, Clp also inclined to decrease biosynthesis of costly tryptophan and vitamin B1 rewarding others. Interestingly, bacterial communication inclined to influence the bacteria with many cooperators in the community or with high capacity to export cofactors for cross-feedings when temperature decreased. As results, these bacteria were enriched which could lead to closer interactions in whole community to adapt to low temperatures. The discovered intelligence of bacterial communication opened another window for understanding bacterial sociobiology.

Evaluation and Validation on Sensitivity of Near-Infrared Diffuse Reflectance in Non-Invasive Human Blood Glucose Measurement.

In non-invasive blood glucose measurement, the sensitivity of glucose-induced optical signals within human tissue is a crucial reference point. This study evaluates the sensitivity of glucose-induced diffuse reflectance in the 1000-1700 nm range. A key factor in understanding this sensitivity is the rate at which the scattering coefficient changes due to glucose, as it is significantly higher than in non-living media and predominantly influences the diffuse light signal level when blood glucose levels change. The study measured and calculated the changes in the scattering coefficient at 1314 nm, a wavelength chosen for its minimal interference from glucose absorption and other bodily constituents. Based on the Mie scattering theory and the results at 1314 nm, the changes in the scattering coefficient within the 1000-1700 nm range were estimated. Subsequently, the sensitivity of the glucose signal across this range was determined through Monte Carlo (MC) simulations. The findings from 25 human trials indicate that the measured sensitivities at five other typical wavelengths within this band generally align with the sensitivities calculated using the aforementioned method. This research can guide the identification of blood glucose signals and the selection of wavelengths for non-invasive blood glucose measurements.

The phytopathogen Xanthomonas campestris senses and effluxes salicylic acid via a sensor HepR and an RND family efflux pump to promote virulence in host plants.

Salicylic acid (SA) plays an essential role in plant defense against biotrophic and semi-biotrophic pathogens. Following pathogen recognition, SA biosynthesis dramatically increases at the infection site of the host plant. The manner in which pathogens sense and tolerate the onslaught of SA stress to survive in the plant following infection remains to be understood. The objective of this work was to determine how the model phytopathogen Xanthomonas campestris pv. campestris (Xcc) senses and effluxes SA during infection inside host plants. First, RNA-Seq analysis identified an SA-responsive operon Xcc4167-Xcc4171, encoding a MarR family transcription factor HepR and an RND (resistance-nodulation-cell division) family efflux pump HepABCD in Xcc. Electrophoretic mobility shift assays and DNase I footprint analysis revealed that HepR negatively regulated hepABCD expression by specifically binding to an AT-rich region of the promoter of the hepRABCD operon, Phep. Second, isothermal titration calorimetry and further genetic analysis suggest that HepR is a novel SA sensor. SA binding released HepR from its cognate promoter Phep and then induced the expression of hepABCD. Third, the RND family efflux pump HepABCD was responsible for SA efflux. The hepRABCD cluster was also involved in the regulation of culture pH and quorum sensing signal diffusible signaling factor turnover. Finally, the hepRABCD cluster was transcribed during the XC1 infection of Chinese radish and was required for the full virulence of Xcc in Chinese radish and cabbage. These findings suggest that the ability of Xcc to co-opt the plant defense signal SA to activate the multidrug efflux pump may have evolved to ensure Xcc survival and virulence in susceptible host plants.

Signal‐Amplifying Biohybrid Material Circuits for CRISPR/Cas‐Based Single‐Stranded RNA Detection

AbstractThe functional integration of biological switches with synthetic building blocks enables the design of modular, stimulus‐responsive biohybrid materials. By connecting the individual modules via diffusible signals, information‐processing circuits can be designed. Such systems are, however, mostly limited to respond to either small molecules, proteins, or optical input thus limiting the sensing and application scope of the material circuits. Here, a highly modular biohybrid material is design based on CRISPR/Cas13a to translate arbitrary single‐stranded RNAs into a biomolecular material response. This system exemplified by the development of a cascade of communicating materials that can detect the tumor biomarker microRNA miR19b in patient samples or sequences specific for SARS‐CoV. Specificity of the system is further demonstrated by discriminating between input miRNA sequences with single‐nucleotide differences. To quantitatively understand information processing in the materials cascade, a mathematical model is developed. The model is used to guide systems design for enhancing signal amplification functionality of the overall materials system. The newly designed modular materials can be used to interface desired RNA input with stimulus‐responsive and information‐processing materials for building point‐of‐care suitable sensors as well as multi‐input diagnostic systems with integrated data processing and interpretation.

Role of diffusible signal factor in regulating aerobic granular sludge formation under temperature shocks

Signal-molecule-mediated strategies are proposed for aerobic granular sludge (AGS), but the regulatory mechanisms behind AGS formation are largely unexplored. In this study, two sequence batch reactors (SBRs) were operated to investigate the regulation of diffusible signal factor (DSF) in AGS formation. DSF secretion in Reactor 2 (R2: 10 °C→25 °C) decreased by 15 % compared to Reactor 1 (R1: 25 °C→10 °C), correlating with a 26 % increase in extracellular polymeric substance (EPS) concentration, resulting in a 63 % acceleration of the granulation process. After temperature shocks in R2, DSF concentration increased by 70 %, while EPS concentration decreased by 47 %. Batch tests confirmed that DSF inhibited EPS secretion. Combined 16S rRNA analysis and machine learning identified key bacteria responsible for secreting EPS and signal molecule. The decrease in the abundances of these bacteria reduced EPS production. These findings on DSF regulation of EPS secretion provide an in-depth understanding of enhanced AGS granulation.

Diffuse scattering from dynamically compressed single-crystal zirconium following the pressure-induced α→ω phase transition

The prototypical α→ω phase transition in zirconium is an ideal test bed for our understanding of polymorphism under extreme loading conditions. After half a century of study, a consensus had emerged that the transition is realized via one of two distinct displacive mechanisms, depending on the nature of the compression path. However, recent dynamic-compression experiments equipped with diffraction diagnostics performed in the past few years have revealed new transition mechanisms, demonstrating that our understanding of the underlying atomistic dynamics and transition kinetics is in fact far from complete. We present classical molecular dynamics simulations of the α→ω phase transition in single-crystal zirconium shock compressed along the [0001] axis using a machine-learning-class potential. The transition is predicted to proceed primarily via a modified version of the two-stage Usikov-Zilberstein mechanism, whereby the high-pressure ω phase heterogeneously nucleates at boundaries between grains of an intermediate β phase. We further observe the fomentation of atomistic disorder at the junctions between β grains, leading to the formation of highly defective interstitial material between the ω grains. We directly compare synthetic x-ray diffraction patterns generated from our simulations with those obtained using femtosecond diffraction in recent dynamic-compression experiments, and show that the simulations produce the same unique, anisotropic diffuse scattering signal unlike any previously seen from an elemental metal. Our simulations suggest that the diffuse signal arises from a combination of thermal diffuse scattering, nanoparticlelike scattering from residual kinetically stabilized α and β grains, and scattering from interstitial defective structures. Published by the American Physical Society 2024

Neuropathological hallmarks in the post-mortem retina of neurodegenerative diseases

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