Biology subjects

Gietl, A.

Publications and source records attributed to Gietl, A..

5 recordsLinked to original sources

bioRxiv2026

Peripheral T-cell co-signalling states mark vulnerability and resilience to cerebral Aβ pathology

Adaptive immune responses may influence vulnerability and resilience in Alzheimers disease (AD), but relevant T-cell states remain unclear. We profiled peripheral immune cells by mass cytometry in 200 participants across distinct age groups, early AD and exceptional old age without dementia, relating immune features to amyloid-{beta} (A{beta}) PET, plasma biomarkers and longitudinal structural and cognitive outcomes. Inducible T-cell co-stimulator (ICOS) expression across CD4 and CD8 memory T-cells was associated with cerebral A{beta} pathology. In mild cognitive impairment (MCI), higher ICOS expression on CD8 memory T-cells strengthened the association between A{beta} load and hippocampal atrophy. A{beta}-derived peptides induced proliferative ICOS+CD25+ memory CD4 and CD8 T-cell responses predominantly in A{beta}-positive participants in an independent cohort. Conversely, higher programmed cell death protein 1 (PD-1) expression on CD8 effector-memory T-cells was associated with attenuated A{beta}-related episodic-memory decline in exceptionally old participants and was higher in stable MCI than in MCI-to-AD converters. These findings identify distinct co-stimulatory and co-inhibitory T-cell correlates of vulnerability and resilience.

immunology↗

bioRxiv2024

Altered T cell reactivity to β-amyloid-related antigens in early Alzheimer's disease

There is growing evidence that the adaptive immune system and neurodegenerative Alzheimers disease (AD) are intertwined in multiple ways. Recent studies have reported alterations of the adaptive immune system in early AD stages, such as preclinical AD and mild cognitive impairment (MCI) due to AD. However, the identity of specific antigenic targets and whether the respective response is beneficial or detrimental during disease progression are still open questions. Herein, we describe cross-sectional analyses of blood and cerebrospinal fluid from three different study populations covering early AD stages. We employed high-dimensional mass cytometry, single-cell RNA-sequencing, in vitro T cell secretome analysis, and antigen presentation assays to achieve a comprehensive characterization of adaptive immune cell populations. Our results show that subjects at the stage of asymptomatic, preclinical AD can mount a CD4+ T helper cell response towards {beta}- amyloid peptide and display an early enrichment of cytotoxic CD8+ effector/TEMRA cells in CSF, combined with a less immunosuppressive gene signature of peripheral regulatory T cells. Conversely, in MCI due to AD, we observed increased frequencies of CD8+ effector/TEMRA cells in the periphery, characterized by a pro-inflammatory gene expression profile and an overall decrease in antigen responsiveness. Our results demonstrate the complexity of adaptive immune changes in early AD and suggest that it may be beneficial in the preclinical stage to promote specific CD4+ T cell responses, while in MCI it may be important to therapeutically target CD8+ T cell responses if these prove to be harmful.

immunology↗

bioRxiv2023

Analysis of skull thickness, scalp-to-cortex distance and association with age and sex in cognitively normal elderly

Personalized neurostimulation has been a potential treatment for many brain diseases, which requires insights into brain/skull geometry. Here, we developed an open source efficient pipeline BrainCalculator for automatically computing the skull thickness map, scalp-to-cortex distance (SCD), and brain volume based on T1-weighted magnetic resonance imaging (MRI) data. We examined the influence of age and sex cross-sectionally in 407 cognitively normal older adults (71.9{+/-}8.0 years, 60.2% female) from the ADNI. We demonstrated the compatibility of our pipeline with commonly used preprocessing packages and found that BrainSuite Skullfinder was better suited for such automatic analysis compared to FSL Brain Extraction Tool 2 and SPM12- based unified segmentation using ground truth. We found that the sphenoid bone and temporal bone were thinnest among the skull regions in both females and males. There was no increase in regional minimum skull thickness with age except in the female sphenoid bone. No sex difference in minimum skull thickness or SCD was observed. Positive correlations between age and SCD were observed, faster in females (0.307%/y) than males (0.216%/y) in temporal SCD. A negative correlation was observed between age and whole brain volume computed based on brain surface (females -1.031%/y, males -0.998%/y). In conclusion, we developed an automatic pipeline for MR-based skull thickness map, SCD, and brain volume analysis and demonstrated the sex-dependent association between minimum regional skull thickness, SCD and brain volume with age. This pipeline might be useful for personalized neurostimulation planning.

neuroscience↗

bioRxiv2023

Early beta-amyloid accumulation in the brain is associated with peripheral T cell alterations

Fast and minimally invasive approaches for early, preclinical diagnosis of neurodegenerative Alzheimers disease (AD) are highly anticipated. Evidence of adaptive immune cells responding to cerebral {beta}-amyloidosis, one of the pathological hallmarks of AD, has raised the question of whether immune markers could be used as proxies for {beta}-amyloid accumulation in the brain. Here, we deploy multidimensional mass cytometry combined with unbiased machine learning techniques to immunophenotype peripheral blood mononuclear cells from study participants in cross-sectional and longitudinal cohorts. We show that increases in antigen-experienced adaptive immune cells in the blood, particularly CD45RA-reactivated T effector memory (TEMRA) cells, are associated with early accumulation of brain {beta}-amyloid and with changes in plasma AD biomarkers in still cognitively healthy subjects. Our results suggest that preclinical AD pathology is linked to systemic alterations of the adaptive immune system. These immunophenotype changes may help in the future to identify and develop novel diagnostic tools for early AD assessment and to better understand clinical outcomes.

immunology↗

bioRxiv2022

Coregistered transcranial optoacoustic and magnetic resonance angiography of the human brain

Imaging modalities capable of visualizing the human brain have led to major advances in neurology and brain research. Multi-spectral optoacoustic tomography (MSOT) has gained importance for studying cerebral function in rodent models due to its unique capability to map changes in multiple hemodynamic parameters and to directly visualize neural activity within the brain. The technique further provides molecular imaging capabilities that can facilitate early disease diagnosis and treatment monitoring. However, transcranial imaging of the human brain is hampered by acoustic attenuation and other distortions introduced by the skull. Here, we demonstrate noninvasive transcranial MSOT angiography through the temporal bone of an adult healthy volunteer. Time-of-flight (TOF) magnetic resonance angiography (MRA) and T1-weighted structural MRI were further acquired to facilitate anatomical registration and interpretation. The superior middle cerebral vein in the temporal cortex was identified in the MSOT images, matching its location observed in the TOF-MRA images. These initial results pave the way toward the application of MSOT in clinical brain imaging.

neuroscience↗