Biology subjects

Andersson, M.

Publications and source records attributed to Andersson, M..

At least 19 recordsLinked to original sources

bioRxiv2025

The molecular architecture of the aquaglyceroporin gating system in Saccharomyces cerevisiae

Aquaglyceroporins have been extensively studied in multiple systems. However, the molecular architecture and hence the precise mechanisms of action remain unknow. The yeast aquaglyceroporin Fps1 plays the main role in controlling cellular turgor. It is regulated by the two Rgc proteins which activate the Fps1 channel. To date, the molecular architecture and dynamics of the Fps1-Rgc gating system is unknown. We employed dual-coloured super-resolution millisecond fluorescence microscopy with a single-molecule sensitivity, to track Fps1 and Rgc2 in real time. Unlike previously believed, our data shows that Rgc2 mainly operates as a homodimer. At the same time, Rgc1, the seemingly redundant regulatory ortholog of Rgc2, has a clear effect on the architecture, colocalisation behaviour and molecular dynamics of the Fps1 and Rgc2 together. Moreover, Rgc1 seems to promote Rgc2 stability in response to hydrogen peroxide stress. Together, our results provide novel insights into the mechanism behind aquaglyceroporins regulation. ImportanceThe components of the Fps1 aquaglyceroporin gating system is conserved in Fungi and present in both bakers yeast Saccharomyces cerevisiae as well as common pathogenic included in the WHO fungal priority pathogens list: Candida albicans, Candida glabrata, Aspergillus fumigatus, Pichia kudriavzevii. For instance, in C. glabrata, the orthologs of both Fps1 and Rgc2 are involved in key pathogenic processes related to acetate tolerance, phagocytosis by macrophages, resistance to antifungal agents and overall drug uptake and efflux. As the Fps1 gating system is not present in metazoans, it constitutes an attractive drug target for antifungal agents. Thus, understanding the architecture and the finer mechanisms of the Fps1 pore regulation is a stepping stone in development of effective antifungal treatment and targeted antifungal drugs.

molecular biology↗

bioRxiv2025

Endospore Appendages Enhance Bacillus cereus Spore Adhesion to Industrial Surfaces, Modulated by Physicochemical Factors

Spores of species belonging to the Bacillus cereus group (B. cereus spp.) are common contaminants in food processing environments due to their ability to adhere to surfaces and resist cleaning procedures. These spores are equipped with pilus-like endospore appendages (ENAs), which are believed to promote surface adhesion. We have investigated the role of ENAs in spore adhesion to abiotic surfaces using wild-type (WT) B. cereus spp. strains and isogenic mutants lacking ENAs or an intact exosporium. WT spores expressing both short and long ENAs (S+L+) adhered significantly more to stainless steel (SS) and polypropylene (PP) compared to bald spores (S-L-) and spores of an exosporium-deficient mutant ({Delta}exsY), while adhesion to polystyrene (PS) and glass was not significantly affected by the presence of ENAs. The {Delta}exsY mutant showed the lowest adhesion across all tested surfaces, a pattern also observed for vegetative cells. The individual roles of S-ENA and L-ENA were also assessed, where the strongest adhesion occurred when both fibers were present on PP. A trend also emerged on PP; WT remained adhered for an hour, while bald spores tended to detach within that time. For saline conditions and pH, bald spores adhered strongly to SS, while for non-ionic surfactant and concentrated protein solutions, WT spores exhibited the strongest adhesion. These results highlight the crucial role of ENAs in B. cereus spp. spore adhesion to industrial relevant surfaces, providing mechanistic insight into spore persistence. This understanding supports the design of surface treatments to prevent contamination, spoilage, and foodborne illness. ImportanceBacteria belonging to the Bacillus cereus group represent a persistent challenge in food production due to their highly resilient endospores (spores), which resist cleaning and disinfection as well as food processing. Understanding the adhesion properties of these spores is essential for designing effective surface treatments that reduce chemical use, enhance food safety and quality, and minimize environmental impact. This study underscores the important role of endospore appendages (ENAs) in spore adhesion to common materials in food processing and laboratory environments. Wild-type spores expressing both S-ENA and L-ENA adhered significantly more than mutants lacking ENAs or the exosporium, highlighting ENAs as potential targets for disrupting spore adhesion. Time-dependent adhesion tests on polypropylene revealed strong, sustained attachment by wild-type spores, contrasting with weaker, transient adhesion by ENA-depleted mutants. These findings offer valuable insights into B. cereus spore adhesion dynamics, guiding the development of tailored cleaning protocols to improve contamination control and sustainability.

microbiology↗

bioRxiv2025

Global brain maintenance predicts well-preserved cognitive function: A pooled analysis of three longitudinal population-based Swedish cohorts

Substantial heterogeneity in cognitive ageing is well documented. Such heterogeneity has been attributed to individual differences in brain maintenance - i.e., the relative preservation of neural resources in ageing. However, large-scale longitudinal evidence is lacking. We pooled data from three population-based Swedish cohorts (Betula, N = 196; SNAC-K, N = 472; H70, N = 688; aged 60-93 years at baseline, follow-up duration up to 7 years) to assess whether global brain maintenance is associated with better preserved cognition in ageing, and to identify lifestyle predictors of brain maintenance. In each cohort, global brain integrity was indexed by the volume of the lateral ventricles (adjusted for total intracranial volume), and general cognitive function based on a principal component analysis of four age-sensitive cognitive domains. Participants were classified into subgroups of low (i.e., aged) versus high (i.e., youth-like) brain integrity based on ventricular volume estimates available for a younger reference sample in one of the cohorts (Betula, 25-55 years, N = 60). Subgroup differences in cognition at baseline and over the follow-up were assessed with ANCOVAs and linear mixed effects models. Logistic regressions were used to examine lifestyle predictors of brain maintenance. Across cohorts, 881 individuals (64.97%) were classified into the high brain integrity subgroup at baseline and 409 individuals (49.82%) over the follow-up. Maintenance of more youth-like brain integrity was associated with better baseline cognition (p < .001) and less cognitive decline longitudinally (p < .001). Moreover, lower cardiovascular disease (CVD) risk and the absence of diabetes predicted brain maintenance at baseline (CVD risk, OR = 0.80, 95% CI [0.68, 0.93]; diabetes, OR = 0.39, 95% CI [0.26, 0.59]) and over the follow-up (CVD risk, OR = 0.79, 95% CI [0.64, 0.96]; diabetes, OR = 0.53, 95% CI [0.29, 0.94]). These findings underscore brain maintenance as a key determinant of cognitive ageing and highlight the importance of managing cardiovascular and metabolic disease risk factors for promotion of brain and cognitive health in later life.

neuroscience↗

bioRxiv2024

Chemotherapy causes a reversible decrease in VMP1/MIR21 DNA methylation in granulocytes from breast cancer survivors

BackgroundDNA methylation alterations within the VMP1/MIR21 gene region, a potential epigenetic biomarker of systemic inflammation, have been demonstrated in mononuclear blood cells from early breast cancer (BC) patients after chemotherapy. Whether these changes are present in granulocytes, persist in the years after treatment, and affect VMP1 or MIR21 gene expression, remains unknown. AimWe aimed to investigate whether adjuvant chemotherapy alters the DNA methylation and gene expression of VMP1/MIR21 in granulocytes from postmenopausal BC patients and, if so, whether these treatment-induced changes are reversible in the first two years after completed chemotherapy. MethodsWhole blood samples were obtained from 30 postmenopausal BC patients before chemotherapy and every six months for two years, and from 10 healthy age- and BMI-matched controls. DNA and RNA was extracted from isolated granulocytes, and DNA methylation of four CpG sites located in the gene body of VMP1, which is situated in the promoter region of MIR21, was assessed through bisulfite pyrosequencing. qPCR was used for assessment of VMP1 and MIR21 expression. ResultsVMP1/MIR21 was significantly demethylated in granulocytes from BC patients shortly after completed chemotherapy compared to before (10 percentage points decrease, p<0.0001). Six months thereafter, DNA methylation values were significantly increased (6 percentage points, p = 0.002), and they were further increased to pre-chemotherapy levels 12, 18 and 24 months post chemotherapy. Chemotherapy did not cause significant changes in the expression of VMP1 or MIR21. ConclusionThe unique follow-up samples in this study demonstrated that chemotherapy induced a transient reduction in DNA methylation of the VMP1/MIR21 region in granulocytes from postmenopausal BC patients. Although transient, chemotherapy-induced epigenetic changes in blood cells may contribute to the increased risk of inflammatory-related comorbidities in BC survivors.

molecular biology↗

bioRxiv2024

The role of endospore appendages in spore-spore contacts in pathogenic bacilli

Species within the spore-forming Bacillus cereus sensu lato group are recognized for their role in food spoilage and food poisoning. B. cereus spores are decorated with numerous pilus-like appendages, called S-ENAs and L-ENAs. These appendages are believed to play crucial roles in self-aggregation, adhesion, and biofilm formation. By using both bulk and single-cell approaches, we investigate the role of S-and L-ENAs as well as the impact of different environmental factors in spore-to-spore contacts and in the interaction between spores and vegetative cells. Our findings reveal that ENAs, and particularly their tip fibrilla, play an essential role in spore self-aggregation but not in the adhesion of spores to vegetative cells. The absence of L-BclA, which builds the L-ENA tip fibrillum, reduced both S-and L-ENA mediated spore aggregation, emphasizing the interconnected roles of S-and L-ENAs. Increased salt concentrations in the liquid environment significantly reduced spore aggregation, implying a charge dependency of spore-spore interactions. By elucidating these complex interactions, our study provides valuable insights into spore dynamics. This knowledge can guide future studies on spore behavior in environmental settings and aids in developing strategies to manage bacterial aggregation for beneficial purposes, like controlling biofilms in food production equipment.

microbiology↗

bioRxiv2024

Evaluating the position of the uncal apex as a predictor of episodic memory across the adult lifespan

Structural decline of the hippocampus follows heterogeneous spatial patterns, and is an important determinant of episodic memory dysfunction in aging. However, evidence indicate that the anatomical landmark uncal apex, used to demarcate anterior and posterior hippocampal subregions, changes position as the hippocampus atrophies. This risks misclassifying gray matter into the incorrect subregion when using standard demarcation methods, potentially contributing to over- and underestimation of age-related anterior and posterior hippocampal volume loss, respectively. Yet, it remains unexplored whether inter-individual differences in uncal apex position itself predict episodic memory performance. Here, we manually identified the uncal apex in anatomical MRI data from a healthy adult-lifespan sample (n=180; 20-79 years), analyzed age differences in its position, and examined associations with word recall performance. Increasing age was linked to a more anteriorly located uncal apex (retracting [~]0.04 mm/year), and this anterior shift was linked to lower memory performance. Using the manually identified uncal apex for subregion segmentation in native space revealed a lower proportion of anterior hippocampal volume compared to segmentation in MNI space (y = -21), with effects of age on volumes differing between methods. Memory performance was not predicted by hippocampal subregion volumes, but the ratio of posterior to anterior volume was significantly linked to memory when accounting for tissue misclassification due to uncal apex variation. These results indicate that uncal apex position may provide an estimate of hippocampal integrity sensitive to inter-individual differences in memory, independent of limitations associated with different segmentation methods.

neuroscience↗

bioRxiv2023

A community-curated, global atlas of Bacillus cereus sensu lato genomes for epidemiological surveillance

The ability to cause foodborne illness, anthrax, and other infections has been attributed to numerous lineages within Bacillus cereus sensu lato (s.l.). However, existing pathogen surveillance databases facilitate dangerous pathogen misidentifications when applied to B. cereus s.l., potentially hindering outbreak or bioterrorism attack response efforts. To address this, we developed BTyperDB (www.btyper.app), an atlas of B. cereus s.l. genomes with standardized, community-curated metadata. BTyperDB aggregates all publicly available B. cereus s.l. genomes (including >2,600 previously unassembled genomes) with novel genomes donated by laboratories around the world, nearly doubling the number of publicly available B. cereus s.l. genomes. To showcase its utility for pathogen surveillance, we use BTyperDB to identify emerging anthrax toxin- and capsule-harboring lineages. Overall, our study provides insight into the epidemiology of an under-studied group of emerging pathogens and highlights the benefits of inclusive, community-driven metadata FAIRification efforts.

microbiology↗

bioRxiv2023

Exploring white matter dynamics and morphology through interactive numerical phantoms: The White Matter Generator

Brain white matter is a dynamic environment that continuously adapts and reorganizes in response to stimuli and pathological changes. Glial cells, especially, play a key role in tissue repair, inflammation modulation, and neural recovery. The movements of glial cells and changes in their concentrations can influence the surrounding axon morphology. We introduce the White Matter Generator (WMG) tool to enable the study of how axon morphology is influenced through such dynamical processes, and how this, in turn, influences the diffusion-weighted MRI signal. This is made possible by allowing interactive changes to the configuration of the phantom generation throughout the optimisation process. The phantoms can consist of axons, myelinated axons, and cell clusters, separated by extra-cellular space. Due to morphological flexibility and computational advantages during the optimisation, the tool uses ellipsoids as building blocks for all structures; chains of ellipsoids for axons, and individual ellipsoids for cell clusters. After optimisation, the ellipsoid representation can be converted to a mesh representation which can be employed in Monte-Carlo diffusion simulations. This offers an effective method for evaluating tissue microstructure models for diffusion-weighted MRI in controlled realistic white matter environments. Hence, the WMG offers valuable insights into white matters adaptive nature and implications for diffusion-weighted MRI microstructure models, and thereby holds the potential to advance clinical diagnosis, treatment, and rehabilitation strategies for various neurological disorders and injuries.

neuroscience↗

bioRxiv2023

Mapping axon diameters and conduction velocity in the rat brain - different methods tell different stories of the structure-function relationship

The structure-function relationship of nerve fibers describes an empirically determined linear relationship between axon diameter, myelin thickness (i.e., g-ratio), and conduction velocity. We investigated the structure-function relationship with different modalities in axons projecting through the corpus callosum of the rodent brain. We measured transcallosal conduction times using optogenetically evoked local field potentials (LFP) and estimated conduction velocity after measuring the callosal length with diffusion magnetic resonance imaging (dMRI) based tractography. Tractography followed the same projection as the fluorescently labeled axons in the corpus callosum. In the same animal, axon diameters were quantified using transmission electron microscopy (TEM) and dMRI. Axon distributions of TEM indicated a bimodal population, where the larger axons shrink more than the smaller ones, when comparing the modes with cryo-TEM. When applying shrinkage-correction to axon diameters from TEM of dehydrated tissue, they were better aligned with estimates from dMRI obtained in the same animal. Measured LFPs predicted axon diameters that agree with the primary mode of the axon distribution, whereas the large axons estimated by dMRI predicted latencies too short to be measured by LFPs. Different modalities show different degrees of variations, being low between animals, suggesting that the variation is methodologically dominated - not anatomically. Our results show that modalities have different sensitivity profiles to the whole axon diameter distribution. Therefore, caution must be taken when interpreting a methods prediction of a metric, as it may not represent the full but only a sub-part of the structure-function relationship of an axonal projection. Significance StatementWe acquire both functional and structural metrics, namely conduction velocity, pathway length, axon diameter, and g-ratio in the same cohort of animals. The transcallosal conduction time was obtained from electrophysiological measurements after contralateral optogenetic stimulation in the rat motor cortex. Cryo-fixation of the tissue reveals different shrinkages for different sub-populations in the diameter distribution. Measured latencies correspond to the small axonal subpopulation with diameters extending up to the mode of the distribution obtained with electron microscopy. Diffusion-MRI primarily appears sensitive to the larger axons, obtained with histology, after correcting for diameter weighting and shrinkage. Different modalities can have very different sensitivities to the structure-function relationship of an axonal projection which must be accounted for in the interpretation.

neuroscience↗

bioRxiv2023

Bridging the 3D geometrical organisation of white matter pathways across anatomical length scales and species

We used diffusion MRI and x-ray synchrotron imaging on monkey and mice brains to examine the organisation of fibre pathways in white matter across anatomical scales. We compared the structure in the corpus callosum and crossing fibre regions and investigated the differences in cuprizone-induced demyelination mouse brains versus healthy controls. Our findings revealed common principles of fibre organisation that apply despite the varying patterns observed across species; small axonal fasciculi and major bundles formed laminar structures with varying angles, according to the characteristics of major pathways. Fasciculi exhibited non-straight paths around obstacles like blood vessels, comparable across the samples of varying fibre complexity and demyelination. Quantifications of fibre orientation distributions were consistent across anatomical length scales and modalities, whereas tissue anisotropy had a more complex relationship, both dependent on the field-of-view. Our study emphasises the need to balance field-of-view and voxel size when characterising white matter features across length scales.

neuroscience↗

bioRxiv2023

Accelerated brain change in healthy adults is associated with genetic risk for Alzheimer's disease and uncovers adult lifespan memory decline

Across healthy adult life our brains undergo gradual structural change in a pattern of atrophy that resembles accelerated brain changes in Alzheimers disease (AD). Here, using four polygenic risk scores for AD (PRS-AD) in a longitudinal adult lifespan sample aged 30 to 89 years (2-7 timepoints), we show that healthy individuals who lose brain volume faster than expected for their age, have a higher genetic AD risk. We first demonstrate PRS-AD associations with change in early Braak regions, namely hippocampus, entorhinal cortex, and amygdala, and find evidence these extend beyond that predicted by APOE genotype. Next, following the hypothesis that brain changes in ageing and AD are largely shared, we performed machine learning classification on brain change trajectories conditional on age in longitudinal AD patient-control data, to obtain a list of AD-accelerated features and model change in these in adult lifespan data. We found PRS-AD was associated with a multivariate marker of accelerated change in many of these features in healthy adults, and that most individuals above [~]50 years of age are on an accelerated change trajectory in AD-accelerated brain regions. Finally, high PRS-AD individuals also high on a multivariate marker of change showed more adult lifespan memory decline, compared to high PRS-AD individuals with less brain change. Our results support a dimensional account linking normal brain ageing with AD, suggesting AD risk genes speed up the shared pattern of ageing- and AD-related neurodegeneration that starts early, occurs along a continuum, and tracks memory change in healthy adults.

neuroscience↗

bioRxiv2023

Susceptibility-induced internal gradients reveal axon morphology and cause anisotropic effects in the dMRI signal

Diffusion-weighted MRI is our most promising method for estimating microscopic tissue morphology in vivo. The signal acquisition is based on scanner-generated external magnetic gradients. However, it will also be affected by susceptibility-induced internal magnetic gradients caused by interaction between the tissue and the static magnetic field of the scanner. With 3D in silico experiments, we show how internal gradients cause morphology-, compartment-, and orientation-dependence of spin-echo and pulsed-gradient spin-echo experiments in myelinated axons. These effects are unseen in previous 2D modelling. For an ex vivo monkey brain, we observe the orientation-dependency generated only when including non-circular cross-sections in the in silico morphological configurations, and find orientation-dependent deviation of up to 17% for diffusion tensor metrics. Our findings underline the importance of accounting for realistic 3D axon morphology in modelling. Interestingly, the morphology-specific orientation-dependency trends show potential for a novel sensitivity to morphology, which is not attainable by the theoretical diffusion-weighted MRI signal itself.

neuroscience↗

bioRxiv2023

A hybrid CNN-Random Forest algorithm for bacterial spore segmentation and classification in TEM images

We present a new approach to segment and classify bacterial spore layers from Transmission Electron Microscopy (TEM) images using a hybrid Convolutional Neural Network (CNN) and Random Forest (RF) classifier algorithm. This approach utilizes deep learning, with the CNN extracting features from images, and the RF classifier using those features for classification. The proposed model achieved 73% accuracy, 64% precision, 46% sensitivity, and 47% F1-score with test data. Compared to other classifiers such as AdaBoost, XGBoost, and SVM, our proposed model demonstrates greater robustness and higher generalization ability for non-linear segmentation. Our model is also able to identify spores with a damaged core as verified using TEMs of chemically exposed spores. Therefore, the proposed method will be valuable for identifying and characterizing spore features in TEM images, reducing labor-intensive work as well as human bias.

microbiology↗

bioRxiv2023

Two long-axis dimensions of hippocampal cortical integration support memory function across the adult lifespan

The hippocampus is a complex structure critically involved in numerous behavior-regulating systems. In young adults, multiple overlapping spatial modes along its longitudinal and transverse axes describe the organization of its functional integration with neocortex, extending the traditional framework emphasizing functional differences between sharply segregated hippocampal subregions. Yet, it remains unknown whether these modes (i.e., gradients) persist across the adult human lifespan, and relate to memory and molecular markers associated with brain function and cognition. In two independent samples, we demonstrate that the principal anteroposterior and second-order, mid-to-anterior/posterior hippocampal modes of neocortical functional connectivity, representing distinct dimensions of macroscale cortical organization, manifest across the adult lifespan. Specifically, individual differences in topography of the second-order gradient predicted episodic memory and mirrored dopamine D1 receptor distribution, capturing shared functional and molecular organization. Older age was associated with less distinct transitions along gradients (i.e., increased functional homogeneity). Importantly, a youth-like gradient profile predicted preserved episodic memory - emphasizing age-related gradient dedifferentiation as a marker of cognitive decline. Our results underscore a critical role of mapping multidimensional hippocampal organization in understanding the neural circuits that support memory across the adult lifespan.

neuroscience↗

bioRxiv2023

The iron-dopamine D1 coupling modulates neural signatures of working memory across adulthood

Brain iron overload and decreased integrity of the dopaminergic system have been independently reported as brain substrates of cognitive decline in aging. Dopamine (DA), and iron are co-localized in high concentrations in the striatum and prefrontal cortex (PFC), but follow opposing age-related trajectories across the lifespan. DA contributes to cellular iron homeostasis and the activation of D1-like DA receptors (D1DR) alleviates oxidative stress-induced inflammatory responses, suggesting a mutual interaction between these two fundamental components. Still, a direct in-vivo study testing the iron-D1DR relationship and their interactions on brain function and cognition across the lifespan is rare. Using PET and MRI data from the DyNAMiC study (n=180, age=20-79, %50 female), we showed that elevated iron content was related to lower D1DRs in DLPFC, but not in striatum, suggesting that dopamine-rich regions are less susceptible to elevated iron. Critically, older individuals with elevated iron and lower D1DR exhibited less frontoparietal activations during the most demanding task, which in turn was related to poorer working-memory performance. Together, our findings suggest that the combination of elevated iron load and reduced D1DR contribute to disturbed PFC-related circuits in older age, and thus may be targeted as two modifiable factors for future intervention. HighlightsO_LIFirst study demonstrating the association between regional iron and dopamine D1DR in adult humans. C_LIO_LIThe interplay between age-related elevated iron and diminished D1DR explained lower task-related brain activity, which in turn was related to poorer task performance. C_LIO_LIOur findings iron-DA coupling can help progress the understanding of the mechanisms behind DA-related neurodegeneration. C_LI

neuroscience↗

bioRxiv2023

Hippocampal subfield volumes contribute to working memory interference control in aging: Evidence from longitudinal associations over 5 years

In memory, familiar but no longer relevant information may disrupt encoding and retrieval of to-be-learned information. While it has been demonstrated that the ability to resolve proactive interference (PI) in working memory (WM) is reduced in aging, the neuroanatomical components of this decline have yet to be determined. Hippocampal (HC) involvement in age- related decline in control of PI is currently not known. In particular, the association between HC subfield volumes and control of PI in WM has not been examined previously. Here we investigate the associations between mean level and 5-year trajectories of gray matter subfield volumes and PI in WM across the adult life span (N = 157). Longitudinal analyses over 5- years across all participants revealed that reduced volume in the subiculum was related to impaired control of PI. Age-stratified analyses showed that this association was most pronounced in older adults. Furthermore, we found that in older adults the effect of age on PI was mediated by GM volume in the HC. The current results show that HC volume is associated with the ability to control PI in WM, and that these associations are modulated by age.

neuroscience↗

bioRxiv2022

Physico-chemical characterization of single bacteria and spores using optical tweezers

Spore-forming pathogenic bacteria are adapted for adhering to surfaces, and their endospores can tolerate strong chemicals making decontamination difficult. Understanding the physico-chemical properties of bacteria and spores is therefore essential in developing antiadhesive surfaces and disinfection techniques. However, measuring physico-chemical properties in bulk does not show the heterogeneity between cells. Characterizing bacteria on a single-cell level can provide mechanistic clues usually hidden in bulk measurements. This paper shows how optical tweezers can be applied to characterize single bacteria and spores, and how physico-chemical properties related to adhesion, fluid dynamics, biochemistry, and metabolic activity can be assessed.

biophysics↗

bioRxiv2022

Bi-phasic patterns of age-related differences in dopamine D1 receptors across the adult lifespan

The dopamine (DA) system, particularly D1-like DA receptors (D1DR), declines across the adult life. The functional consequences of reduced D1DR has been hypothesized to vary across life periods, but the precise timing of these periods is unknown. To examine distinct phases in age-related D1DR reductions, we studied 180 healthy adults (90 females, 20-80 years), who underwent D1DR PET assessment using [11C]SCH23390. A bi-phasic pattern of age-related D1DR differences was revealed, with an inflection point at approximately 40 years of age. Notably, D1DR levels before and after the inflection showed opposing relations to neurocognitive functions, in concordance with distinct consequences of D1DR differences during development and in old age. Furthermore, D1DR reductions in later life were linked to age-related cerebrovascular consequences. These results support a distinction between D1DR reductions in early adulthood from those later in life, and suggest less dramatic and more malleable DA losses in aging than previously suggested.

neuroscience↗