Biology subjects

Rominger, A.

Publications and source records attributed to Rominger, A..

16 recordsLinked to original sources

bioRxiv2026

Fast and Accurate Photon-Transport Modeling based on Foundation-Model-Encoded Implicit Neural Surrogate towards Optimized Near-Infrared Brain Stimulation

Clinical treatment planning for near-infrared (NIR) neuromodulation requires patient-specific dosimetry to optimize light fluence (LF) delivery to cortical targets. The gold-standard Monte Carlo photon-transport forward solver is accurate but computationally expensive and non-differentiable for personalized inverse design across subjects. Here, we present PhomiNeuro, a foundation-model-encoded differentiable surrogate for time-resolved LF modeling and pathology-guided inverse design. A pretrained 3D medical imaging foundation model (VISTA3D) was domain-adapted to 285 training head models annotated with optical properties, and then coupled to an implicit neural representation (INR) that predicts LF at arbitrary spatiotemporal coordinates. Regularized by a time-dependent diffusion-equation residual, it demonstrated superior fidelity in 84 held-out participants, and ablations identified VISTA3D-derived anatomical priors as dominant and physics regularization as complementary. PhomiNeuro enables fast and robust queries of LF and its gradients with respect to illumination parameters for targets guided by individual structural magnetic resonance imaging and amyloid positron emission tomography, achieving 466-fold per-iteration speedup and 167-fold end-to-end optimization speedup. Explanatory analyses of LF delivery variability, including sex differences and amyloid status, identified structural variations as the primary drivers. These results position PhomiNeuro as a highly extensible translational framework toward personalized treatment planning and digital twin development in precision neuromodulation.

bioengineering↗

bioRxiv2026

Divergent scalp-to-region distance alteration patterns in autism spectrum disorders, Parkinson's disease and Alzheimer's disease

Brain stimulation is increasingly recognized as an effective and important therapeutic intervention for many brain diseases. Distance between the scalp and other brain regions is a pivotal variable for neurostimulation planning and the development of new techniques, but alterations in the distance between the scalp and other regions in brain diseases are largely unknown. In this study, we developed an automatic pipeline to calculate scalp-to-region distance (SRD) values from T1 MR images and applied it to a total of 1382 participants, including patients with autism spectrum disorder (ASD), Parkinsons disease (PD), Alzheimers disease (AD), and cognitively normal controls (CNs). Cloud points were uniformly sampled on the automatically extracted scalp surface and cortex surface, on which the point-wise distance maps were generated. The brain was then coregistered with the BCI-DNI atlas, and SRD value for each brain region was extracted. Analysis of covariance (ANCOVA) was performed for SRD in each brain region, with age and sex as covariates. Compared with CNs, ASD patients showed widespread SRD decreases across the brain with prominent involvement of the frontal lobe, especially the orbitofrontal cortex and adjacent regions. In contrast, in AD patients, significantly increased SRD values were observed in various regions of the frontal gyrus. No significant SRD alteration was found in PD patients after correction. The automatic SRD calculation pipeline and the different patterns of SRD alterations in these diseases might be helpful for future neurostimulation planning in clinical practice. HighlightsO_LIAutomatic pipeline enables scalp-to-region distance (SRD) measurement, facilitates brain stimulation planning. C_LIO_LIASD patients show widespread SRD decreases, especially in the orbitofrontal cortex and adjacent regions. C_LIO_LIAD patients present increased SRD in the frontal gyrus and decreased SRD in the parahippocampal gyrus. C_LI

neuroscience↗

bioRxiv2025

Enhanced ex vivo 3D whole-brain mapping and automated analysis of Parkinson's disease pathologies in mice

The spatiotemporal relationships among -synuclein inclusion formation, dopaminergic degeneration, and white matter microstructural changes remain poorly defined. To address this, we unilaterally injected preformed fibrils (PFFs) or monomeric -synuclein into the substantia nigra pars compacta (SNc) of wild-type mice. At 12 and 20 weeks post-injection (wpi), we performed ex vivo magnetic resonance imaging (MRI) at 9.4T to assess microstructural, volumetric and paramagnetic changes, along with light-sheet microscopy (LSM) to map -synuclein aggregates, and dopaminergic neuron at single-cell resolution across the whole brain. We developed a Python-based, automated registration pipeline that achieves <40 {micro}m alignment error between ex vivo MRI and LSM and computes clearing-induced distortion, enabling scalable deformation analysis and multimodal multiscale data integration. Unilateral SNc injection of -syn PFFs induced dense phospho--syn pathology in the ipsilateral SNc at 12 wpi, which decreased by 20 wpi in parallel with the loss of tyrosine hydroxylase-positive dopaminergic neuron. Pathogenic -synuclein spreads along with dopaminergic denervation in the nigrostriatal pathway to the ipsilateral striatum and contralateral SNc. Our ex vivo MRI-LSM platform provides a scalable, open-source framework for understanding circuit-level and whole-brain propagation of pathology in an -synucleinopathy model and beyond. HighlightsO_LIOpen-source, automated pipeline aligns ex vivo 9.4T MRI with light-sheet microscopy (LSM) at <40 {micro}m error, quantifies clearing-induced tissue distortion, and enables multiscale, whole-brain multimodal analysis. C_LIO_LIWhole-brain, single-cell-resolution mapping of -synuclein pathology and dopaminergic neuron loss in an -synucleinopathy mouse model using an optimized iDISCO+ protocol that achieves uniform antibody penetration even in dense regions like the striatum. C_LIO_LIUnilateral SNc injection of -syn PFFs drives spread of p--syn pathology along the nigrostriatal pathway to the ipsilateral striatum, BST, CEA, and contralateral SNc, along with dopaminergic degeneration. C_LIO_LIIpsilateral SNc shows high pS129 pathology at 12 weeks post-injection but significant reduction by 20 wpi, concurrent with loss of tyrosine hydroxylase-positive neurons. C_LIO_LIMultiparametric MRI reveals microstructural and iron-related alterations in striatum, SNc, and VTA, with cross-modal correlations linking pS129 burden, TH loss, and magnetic susceptibility changes. C_LI

neuroscience↗

bioRxiv2025

Reduced levels of synaptic vesicle protein 2A in the extracellular vesicles and brain of Alzheimer's disease- associations with Aβ, tau and synaptophysin

BackgroundSynaptic dysfunction plays an important role in Alzheimers disease (AD) and is an emerging imaging and fluid biomarker. Here, we aimed to assess the regional expression of synaptic vesicle glycoprotein 2A (SV2A) in the brain and extracellular vesicles of AD patients and its associations with the APOE {varepsilon}4 allele, amyloid-{beta}, tau pathologies, and other synaptic markers. MethodsMass spectrometry-based synaptosome proteomics was performed on brain-derived extracellular vesicles (BdEVs) isolated from the frontal cortex of 17 AD patients and 4 NCs. Immunohistochemical staining for SV2A, synaptophysin, amyloid-{beta} and phospho-tau was performed on postmortem tissue from the frontal, temporal, and entorhinal cortices and hippocampus of 40 AD patients and 44 nondemented controls (NCs). ResultsReduced levels of synaptic proteins, including synaptotagamin, GAP43, SYT1, SNAP25 and 14-3-3{zeta}, were positively correlated with SV2A and negatively correlated with GFAP and NEFL in BdEVs from AD patients and NCs. We detected lower levels of SV2A in the hippocampus and entorhinal cortex of AD compard to NCs, and in APOE {varepsilon}4 carriers than in noncarriers. SV2A levels were positively correlated with synaptophysin and negatively correlated with the levels of the amyloid-{beta}, phospho-tau, and Braak stages. ConclusionsThis study provides postmortem evidence of synaptic markers and reduced regional levels of SV2A in brain tissue slices and BdEVs from AD patients compared with NCs and in APOE {varepsilon}4 carriers compared to non-carriers. SV2A could serve as a valuable marker for monitoring synaptic degeneration in AD.

neuroscience↗

bioRxiv2024

Hippocampal mGluR5 levels are comparable in Alzheimer's and control brains, and divergently influenced by amyloid and tau in control brain

BackgroundMetabotropic glutamate receptor 5 (mGluR5) modulates excitatory glutamatergic synaptic transmission and plays an important role in learning and memory formation and in neurodegeneration and amyloid deposition in Alzheimers disease (AD). Conflicting results on the cerebral mGluR5 levels in AD have been reported based on in vivo and postmortem studies. Here, we aimed to assess alterations in hippocampal mGluR5 expression in AD, and the associations between mGluR5 expression and pathologies. MethodsImmunofluorescence staining for mGluR5 was performed on postmortem brain tissue from 34 AD patients and 31 nondemented controls (NCs) and from aged 3xTg and arcA{beta} model mice of AD. Autoradiography was performed on brain tissue slices from arcA{beta} mice using mGluR5 tracer [18F]PSS232. Analysis of different cellular source of GRM5 RNA in human and mouse brains was performed. Proteomic profiling and pathway analysis were performed on hippocampal tissue from aged 3xTg mice and wild-type mice. ResultsNo differences in hippocampal mGluR5 expression or entorhinal cortical GRM5 RNA levels were detected between the AD and NC groups. Hippocampal mGluR5 levels increased with Braak stage and decreased with amyloid level in the NC group. No correlations were detected between the levels of mGluR5 and amyloid, tau, or Iba1/P2X7R in the hippocampus of AD patients and NC cases. Ex vivo autoradiography revealed comparable cerebral levels of [18F]PSS232 in arcA{beta} mice compared to nontransgenic mice. GO and KEGG pathway enrichment analyses revealed that the Shank3, Grm5 and glutamatergic pathways were upregulated in hippocampal tissue from aged 3xTg mice compared to wild-type mice. ConclusionThis study revealed no difference in hippocampal mGluR5 levels between AD patients and NCs and revealed the divergent influence of amyloid and tau pathologies on hippocampal mGluR5 levels in NCs. Species differences were observed in the GRM5 RNA level as well as at the cellular location. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=141 SRC="FIGDIR/small/595868v1_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@17c69aorg.highwire.dtl.DTLVardef@efbaf9org.highwire.dtl.DTLVardef@dc3c2corg.highwire.dtl.DTLVardef@f27038_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2024

Hippocampal purinergic P2X7 receptor level is increased in Alzheimer's disease patients, and associated with amyloid and tau pathologies

INTRODUCTIONThe purinergic receptor P2X7R, which is expressed on microglia and astrocytes, plays an important role in Alzheimers disease (AD). We aimed to characterize the alterations in P2X7R expression in AD patients by APOE {varepsilon}4 allele, age and sex, as well as its association with amyloid and tau pathology. METHODSP2X7R staining and quantitative analysis of amyloid, tau, astrocytes and microglia were performed on postmortem hippocampal tissues from 35 AD patients; 31 nondemented controls; caudate/putamen tissue from corticobasal degeneration (CBD), progressive supranuclear palsy (PSP) patients; and bran tissue from aged 3xTg mouse model of AD. RESULTSActivated microglia and reactive astrocytes were observed in the hippocampi of AD patients and exhibited altered morphology with denser cells and pronounced ramifications. Hippocampal P2X7R intensity was greater in the hippocampal subfields of AD patients than in those of nondemented controls and was correlated with amyloid level and Braak stage and was not affected by sex, APOE{varepsilon}4 allele, or age. P2X7R expression increased around A{beta} plaques, cerebral amyloid angiopathy, tau inclusions in the hippocampus from AD patients and tau inclusions in the caudate/putamen from CBD and PSP patients. DISCUSSIONWe found an increased hippocampal P2X7R level in AD compared to non-demented control, which correlated with amyloid and tau pathologies. P2X7R is a potential marker for neuroinflammation in AD.

neuroscience↗

bioRxiv2024

Increased regional P2X7R expression detected by GSK1482160 PET in a tauopathy mouse model

Neuroinflammation plays an important role in Alzheimers disease and primary tauopathies. The aim of the current study was to map [18F]GSK1482160 for imaging of purinergic P2X7R in Alzheimers disease and primary tauopathy mouse models. MicroPET was performed using [18F]GSK1482160 in widely used mouse models of Alzheimers disease (APP/PS1, 5xFAD and 3xTg), 4-repeat tauopathy (rTg4510) mice and age-matched wild-type mice. Increased uptake of [18F]GSK1482160 was observed in the cortex and basal forebrain of 7-month-old rTg4510 mice compared to age-matched wild-type mice and compared to 3-month-old rTg4510 mice. Nonparametric Spearmans rank analysis revealed a positive correlation between tau [18F]APN-1607 uptake and [18F]GSK1482160 in the hippocampus of rTg4510 mice. No significant differences in the uptake of [18F]GSK1482160 were observed between wild-type mice and APP/PS1 mice (5, 10 months), 5xFAD mice (3, 7 months) or 3xTg mice (10 months). Immunofluorescence staining further indicated the distribution of P2X7Rs in the brains of 7-month-old rTg4510 mice with accumulation of tau inclusion compared to wild-type mice. These findings provide in vivo imaging evidence for increased P2X7R in the brains of tauopathy model mice.

neuroscience↗

bioRxiv2023

Reduced SV2A and GABAA receptor levels in the brains of type 2 diabetic rats revealed by flumazenil PET

PurposeType 2 diabetes mellitus (T2DM) is associated with a greater risk of Alzheimers disease. Synaptic impairment and protein aggregates have been reported in the brains of T2DM models. Here, we assessed whether neurodegenerative changes in synaptic vesicle 2A (SV2A), {gamma};-aminobutyric acid type A (GABAA) receptor, amyloid-{beta}, tau and receptor for advanced glycosylation end product (RAGE) can be detected in vivo in T2DM rats. MethodsPositron emission tomography (PET) using [18F]SDM-8 (SV2A), [18F]flumazenil (GABAA receptor), [18F]florbetapir (amyloid-{beta}), [18F]PM-PBB3 (tau), and [18F]FPS-ZM1 (RAGE) was carried out in 12-month-old diabetic Zucker diabetic fatty (ZDF) and Sprague{square}Dawley (SD) rats. Proteomic profiling and pathway analysis of the hippocampus of ZDF and SD rats were performed. ResultsReduced cortical [18F]SDM-8 and cortical and hippocampal [18F]flumazenil uptake were observed in 12-month-old ZDF rats compared to SD rats. [18F]florbetapir and [18F]PM-PBB3 uptake were comparable in the brains of 12-month-old ZDF rats and SD rats. ConclusionThe findings provide in vivo evidence for regional reductions in SV2A and GABAA receptor levels in the brains of aged T2DM ZDF rats.

neuroscience↗

bioRxiv2023

Relationship between reactive astrocytes, by SMBT-1 imaging, with amyloid-beta, tau, glucose metabolism, and microgliosis in mouse models of Alzheimer's disease

PurposeReactive astrocytes play an important role in the development of Alzheimers disease (AD). Here, we aim to investigate the temporospatial relationship between reactive astrocytes, tau and amyloid-{beta}, glucose metabolism, and microgliosis by using multitracer imaging in AD transgenic mouse models. MethodsPositron emission tomography (PET) imaging with [18F]SMBT-1 (monoamine oxidase-B), [18F]florbetapir (A{beta}), [18F]PM-PBB3 (tau), [18F]FDG, and [18F]DPA-714 (translocator protein) was carried out in 5- and 10-month-old APP/PS1, 11-month-old 3xTg mice, and aged-matched wild-type mice. The brain regional referenced standard uptake value (SUVR) was computed with the cerebellum as the reference region. Immunofluorescence staining was performed in mouse brain tissue slices. Results[18F]SMBT-1 and [18F]florbetapir SUVRs were higher in the cortex and hippocampus of 10-month-old APP/PS1 mice than in 5-month-old APP/PS1 mice and wild-type mice. Reduced [18F]FDG SUVR was observed in the thalamus and midbrain of 5-month-old APP/PS1 mice compared to wild-type mice. No significant difference in brain regional [18F]DPA-714 SUVR was observed in 5- and 10-month-old APP/PS1 mice compared to wild- type mice. No significant difference in the SUVRs of any tracers was observed in 11-month-old 3xTg mice compared to age-matched wild-type mice. A positive correlation between the SUVRs of [18F]SMBT-1 and [18F]DPA-714 in the cortex was observed. Immunostaining validated the distribution of MAO-B and TSPO, amyloid and tau inclusions in brain tissue from 10-month-old APP/PS1 mice and limited changes in 11-month- old 3xTg mice. ConclusionThe findings provide in vivo evidence for reactive astrocytes along with amyloid plaque and tau deposition preceding microgliosis in animal models of AD pathologies.

neuroscience↗

bioRxiv2023

Visualizing alpha-synuclein and iron deposition in M83 mouse model of Parkinson's disease in vivo

BackgroundAbnormal alpha-synuclein and iron accumulation in the brain play an important role in Parkinsons disease (PD). Herein, we aim at visualizing alpha-synuclein inclusions and iron deposition in the brains of M83 (A53T) mouse models of PD in vivo. MethodsFluorescently labelled pyrimidoindole-derivative THK-565 was characterized by using recombinant fibrils and brains from 10-11 months old M83 mice, which subsequently underwent in vivo concurrent wide-field fluorescence and volumetric multispectral optoacoustic tomography (vMSOT) imaging. The in vivo results were verified against structural and susceptibility weighted imaging (SWI) magnetic resonance imaging (MRI) at 9.4 Tesla and scanning transmission X-ray microscopy (STXM) of perfused brains. Brain slice immunofluorescence and Prussian blue staining were further performed to validate the detection of alpha-synuclein inclusions and iron deposition in the brain, respectively. ResultsTHK-565 showed increased fluorescence upon binding to recombinant alpha-synuclein fibrils and alpha-synuclein inclusions in post-mortem brain slices from patients with Parkinsons disease and M83 mice. i.v. administration of THK-565 in M83 mice showed higher cerebral retention at 20 and 40 minutes post-injection by wide-field fluorescence compared to non-transgenic littermate mice, in congruence with the vMSOT findings. SWI/phase images and Prussian blue indicated the accumulation of iron deposits in the brains of M83 mice, presumably in the Fe3+ form, as evinced by the STXM results. ConclusionWe demonstrated in vivo mapping of alpha-synuclein by means of non-invasive epifluorescence and vMSOT imaging assisted with a targeted THK-565 label and SWI/STXM identification of iron deposits in M83 mouse brains ex vivo.

neuroscience↗

bioRxiv2023

Efficient characterization of multiple binding sites of small molecule imaging ligands on amyloid-beta, 4-repeat/full-length tau and alpha-synuclein

AimThere is an unmet need for compounds that detect alpha-synuclein (Syn) and 4-repeat tau, which are critical in many neurodegenerative diseases for diagnostic and therapeutic purposes. Here, we aim to develop an efficient surface plasmon resonance (SPR)-based method to facilitate the characterization of small molecule ligands/compounds to these fibrils. MethodsSPR measurements were conducted to characterize the binding properties of fluorescent ligands/compounds towards recombinant A{beta}42, K18 4-repeat/full-length tau and Syn fibrils. In silico modelling was performed to examine the binding pockets of ligands on Syn fibrils. Immunofluorescence staining with fluorescence ligands and specific antibodies on postmortem brain tissue slices from patients with Parkinsons disease and disease mouse models was performed. ResultsWe optimized the protocol for immobilizing A{beta}42, K18 tau, full-length tau and Syn fibrils in a controlled aggregation state on SPR sensor chips. The results from the analysis of binding kinetics suggested the presence of at least two binding sites for all fibrils, including luminescent conjugated oligothiophenes (HS-169, HS-84, h-FTAA and q-FTAA), pyridine derivative PBB5, nonfluorescent methylene blue and lansoprazole. In silico modelling studies for Syn (6H6B) showed four binding sites with preference to S4. Immunofluorescence staining validated the detection of pS129-positive Syn in brain tissue from Parkinsons disease patients, Syn PFF-injected mice, 6E10-positive A{beta} in arcA{beta} mice, and AT-8/AT-100-positive in tau pR5 tau mice, respectively. ConclusionsSPR measurements of ligands and small molecules binding to A{beta}42, 4R and full-length tau and Syn fibrils suggest the existence of multiple binding sites. This approach may provide efficient characterization of compound binding properties towards these fibrils important in neurodegenerative diseases.

pharmacology and toxicology↗

bioRxiv2022

Multiple paths towards repeated phenotypic evolution in the spiny-leg adaptive radiation (Tetragnatha; Hawaii)

The repeated evolution of phenotypes is ubiquitous in nature and offers some of the clearest evidence of the role of natural selection in evolution. The genomic basis of repeated phenotypic evolution is often complex and can arise from a combination of gene flow, shared ancestral polymorphism and de novo mutation. Here, we investigate the genomic basis of repeated ecomorph evolution in the adaptive radiation of the Hawaiian spiny-leg Tetragnatha. This radiation comprises four ecomorphs that are microhabitat-specialists, and differ in body pigmentation and size (Green, Large Brown, Maroon, and Small Brown). Using 76 newly generated low-coverage, whole-genome resequencing samples, coupled with population genomic and phylogenomic tools, we studied the evolutionary history of the radiation to understand the evolution of the spiny-leg lineage and the genetic underpinnings of ecomorph evolution. Congruent with previous works, we find that each ecomorph has evolved twice, with the exception of the Small Brown ecomorph, which has evolved three times. The evolution of the Maroon and the Small Brown ecomorphs likely involved ancestral hybridization events, whereas the Green and the Large Brown ecomorphs likely evolved because of either standing genetic variation or de novo mutation. Pairwise comparisons of ecomorphs based on the fixation index (FST) show that divergent genomic regions include genes with functions associated with pigmentation (melanization), learning, neuronal and synapse activity, and circadian rhythms. These results show that the repeated evolution of ecomorphs in the Hawaiian spiny-leg Tetragnatha is linked to multiple genomic regions and suggests a previously unknown role of learning and circadian rhythms in ecomorph.

evolutionary biology↗

bioRxiv2021

Pre-therapeutic Microglia Activation and Sex Determine Therapy Effects of Chronic Immunomodulation

Modulation of the innate immune system is emerging as a promising therapeutic strategy against Alzheimers disease (AD). However, determinants of a beneficial therapeutic effect are ill-understood. Thus, we investigated the potential of 18 kDa translocator protein positron-emission-tomography (TSPO-PET) for assessment of microglial activation in mouse brain before and during chronic immunomodulation. Serial TSPO-PET was performed during five months of chronic microglia modulation by stimulation of peroxisome proliferator-activated receptor (PPAR)-{gamma} with pioglitazone in two different mouse models of AD (PS2APP, AppNL-G-F). Using mixed statistical models on longitudinal TSPO-PET data, we tested for effects of therapy and sex on treatment response. We tested correlations of baseline with longitudinal measures of TSPO-PET, and correlations between PET results with spatial learning performance and {beta}-amyloid accumulation of individual mice. Immunohistochemistry was used to determine the molecular source of the TSPO-PET signal. Pioglitazone-treated female PS2APP and AppNL-G-F mice showed attenuation of the longitudinal increases in TSPO-PET signal when compared to vehicle controls, whereas treated male AppNL-G-F mice showed the opposite effect. Baseline TSPO-PET strongly predicted changes in microglial activation in treated mice (R=-0.874, p<0.0001) but not in vehicle controls (R=-0.356, p=0.081). Reduced TSPO-PET signal upon treatment was associated with better spatial learning and higher fibrillar {beta}-amyloid accumulation. Immunohistochemistry confirmed activated microglia to be the source of the TSPO-PET signal (R=0.952, p<0.0001). TSPO-PET represents a sensitive biomarker for monitoring of immunomodulation and closely reflects activated microglia. Pre-therapeutic assessment of baseline microglial activation and sex are strong predictors of individual immunomodulation effects and could serve for responder stratification.

neuroscience↗

bioRxiv2021

Chronic PPARγ Stimulation Shifts Amyloidosis to Higher Fibrillarity but Improves Cognition

BackgroundWe undertook longitudinal {beta}-amyloid positron emission tomography (A{beta}-PET) imaging as a translational tool for monitoring of chronic treatment with the peroxisome proliferator-activated receptor gamma (PPAR{gamma}) agonist pioglitazone in A{beta} model mice. We thus tested the hypothesis this treatment would rescue from increases of the A{beta}-PET signal while promoting spatial learning and preservation of synaptic density. MethodsPS2APP mice (N=23; baseline age: 8 months) and AppNL-G-F mice (N=37; baseline age: 5 months) were investigated longitudinally for five months using A{beta}-PET. Groups of mice were treated with pioglitazone or vehicle during the follow-up interval. We tested spatial memory performance and confirmed terminal PET findings by immunohistochemical and biochemistry analyses. ResultsSurprisingly, A{beta}-PET and immunohistochemistry revealed a shift towards higher fibrillary composition of A{beta}-plaques during upon chronic pioglitazone treatment. Nonetheless, synaptic density and spatial learning were improved in transgenic mice with pioglitazone treatment, in association with the increased plaque fibrillarity. ConclusionThese translational data suggest that a shift towards higher plaque fibrillarity protects cognitive function and brain integrity. Increases in the A{beta}-PET signal upon immunomodulatory treatments targeting A{beta} aggregation can thus be protective.

neuroscience↗

bioRxiv2021

Detecting the ecological footprint of selection

The structure of communities is influenced by many ecological and evolutionary processes, but the way this manifests in classic biodiversity patterns often remains unclear. Here, we aim to distinguish the ecological footprint of selection - through competition or environmental filtering - from that of neutral processes that are invariant to species identity. We build on existing Massive Eco-evolutionary Synthesis Simulations (MESS), which uses information from three biodiversity axes - species abundances, genetic diversity, and trait variation - to distinguish between mechanistic processes. In order to correctly detect and characterise competition, we add a new and more realistic form of competition that explicitly compares the traits of each pair of individuals. Our results are qualitatively different to those of previous work in which competition is based on the distance of each individuals trait to the community mean. We find that our new form of competition is easier to identify in empirical data compared to the alternatives. This is especially true when trait data are available and used in the inference procedure. Our findings hint that signatures in empirical data previously attributed to neutrality may in fact be the result of pairwise-acting selective forces. We conclude that gathering more different types of data, together with more advanced mechanistic models and inference as done here, could be the key to unravelling the mechanisms of community assembly.

ecology↗

bioRxiv2020

A unified model of species abundance, genetic diversity, and functional diversity revealsthe mechanisms structuring ecological communities

Biodiversity accumulates hierarchically by means of ecological and evolutionary processes and feedbacks. Reconciling the relative importance of these processes is hindered by current theory, which tends to focus on a single spatial, temporal or taxonomic scale. We introduce a mechanistic model of community assembly, rooted in classic island biogeography theory, which makes temporally explicit joint predictions across three biodiversity data axes: i) species richness and abundances; ii) population genetic diversities; and iii) trait variation in a phylogenetic context. We demonstrate that each data axis captures information at different timescales, and that integrating these axes enables discriminating among previously unidentifiable community assembly models. We combine our massive eco-evolutionary synthesis simulations (MESS) with supervised machine learning to fit the parameters of the model to real data and infer processes underlying how biodiversity accumulates, using communities of tropical trees, arthropods, and gastropods as case studies that span a range of spatial scales.

evolutionary biology↗