About

Katrin Andreasson is a researcher investigating the role that innate immune responses play in the initiation and progression of neurological diseases. Her work emphasizes recent advances in human genetics, particularly for neurodegenerative disorders like Alzheimer’s disease, highlighting a causal role for a disrupted immune response in disease pathogenesis. Her research suggests that an injurious immune response may be a common factor across many neurological disorders, both acute, such as brain trauma or stroke, and chronic, including epilepsy, Parkinson’s disease, and Alzheimer’s disease. Through a systems biology approach, Dr. Andreasson’s lab is identifying novel immune pathways that may be critical in maladaptive brain inflammation. Her research aims to understand how innate immune responses cause neurodegeneration and circuit disruption, with a focus on immune cell metabolism and the influence of metabolic regulators of immune function. Her objectives include understanding how aberrant CNS and peripheral innate immune responses contribute to synapse loss and circuit vulnerability in neurodegenerative disorders, and developing preventive and therapeutic strategies targeting these inflammatory pathways.

Research topics

• Medicine
• Biology
• Internal medicine
• Genetics
• Immunology
• Cancer research
• Computational biology
• Neuroscience
• Bioinformatics
• Endocrinology
• Cell biology
• Biochemistry
• Pathology

Selected publications

• Organ aging signatures in the plasma proteome track health and disease

  Nature · 2023 · 534 citations

  • Biology
  • Medicine
  • Physiology

  ), the current best blood-based biomarker for AD. Our models link vascular calcification, extracellular matrix alterations and synaptic protein shedding to early cognitive decline. We introduce a simple and interpretable method to study organ aging using plasma proteomics data, predicting diseases and aging effects.

  DOI

• Reduced expression of the cell intrinsic clock protein, Bmal1, in myeloid cells accelerates cognitive decline and alters microglial function in aging mice

  The FASEB Journal · 2021

  Senior authorCorresponding
  • Biology
  • Neuroscience
  • Endocrinology

  The circadian clock system plays a fundamental role in the temporal coordination of the external environment with internal physiological processes. These processes include the sleep/wake cycle, feeding, liver function, kidney function, core body temperature, including insulin release and heart rate, and immune function. With aging, the ability to rhythmically regulate these processes progressively declines. Furthermore, aging is associated with a chronic inflammation that is linked to multiple age‐associated diseases, including cognitive decline. Several studies have demonstrated that deletion of Bmal1, a transcription factor and principal driver of cell‐autonomous circadian rhythms, accelerates the aging process, exhibiting a variety of age‐related diseases including sarcopenia, cataracts, organ shrinkage, bone calcification, and impaired glucose metabolism. Here, we show that myeloid‐lineage specific knockdown of Bmal1 increases systemic inflammation and accelerates cognitive decline in aging mice. This was associated with a paradoxical increase in IBA1 expression and number of microglia with less morphological complexity and reduced lysosomal CD68 in the CA1 hippocampal region. Looking at individual microglia showed less CD68 in the Bmal1‐deficient microglia, suggesting lysosomal dysfunction. Furthermore, myeloid Bmal1 deletion led to significant increases in pre‐ and post‐synaptic proteins in aged mice, as well as decreased levels of C1q, which is required for synaptic pruning, suggesting impaired synapse clearance. In summary, our data indicates that Bmal1 knock‐down in myeloid‐lineage cells is sufficient to accelerate cognitive decline by a mechanism that may involve impaired synapse removal.

  DOI

• FSMP-17. GLOBAL METABOLOMIC PROFILING OF GLIOBLASTOMA MULTIFORME REVEALS METABOLIC VULNERABILITIES IN RESPONSE TO RADIATION THERAPY

  Neuro-Oncology Advances · 2021 · 1 citations

  • Cancer research
  • Biology
  • Computational biology

  Abstract Glioblastoma multiforme (GBM), the most aggressive primary brain tumor, originates in astrocytes and oligodendrocytes and yields a median survival time of less than 2 years and a 5-year survival of 2.5%. There has been little in the way of treatments and novel approaches are needed to combat the poor prognosis of GBM. Recent studies have established that GBM cells exhibit metabolic reprogramming to adapt to diverse metabolic gradients within heterogenous tumor microenvironments. Using an unbiased metabolomics approach, we investigated metabolic changes both pre- and post-ionizing radiation across several patient-derived GBM cell lines. Surprisingly, acute high dosage of ionizing radiation resulted in significant changes in the synthesis of aminolevulinic acid (ALA), a non-proteinogenic amino acid. Fractionation of radiation therapy resulted in dose-dependent changes in the heme synthesis pathway within these cells. Using an orthotopic xenograft mouse model of GBM, we identify several enzymatic vulnerabilities in vivo and discuss a novel combinatorial therapeutic approach of radiation and targeted pharmacological intervention. Our findings reveal the fundamental biosynthetic changes that GBMs adopt when exposed to ionizing irradiation as well as the benefits of a combinatorial approach.

  DOI

• Aging disrupts circadian gene regulation and function in macrophages

  Nature Immunology · 2021 · 159 citations

  • Biology
  • Cell biology
  • Immunology
  DOI

• TREM1-PET imaging of pro-inflammatory myeloid cells distinguishes active disease from remission in Multiple Sclerosis

  Journal of Nuclear Medicine · 2020 · 2 citations

  • Medicine
  • Immunology
  • Pathology

  199 Objectives: Although multiple disease-modifying immunomodulatory therapies are available for relapsing-remitting multiple sclerosis (RR-MS)1, therapeutic selection and monitoring is hampered by the lack of sensitive central nervous system (CNS) immune biomarkers. Increasing evidence indicates that the presence, extent, and spatiotemporal dynamics of activated myeloid cells (i.e., macrophages, microglia, monocytes, neutrophils, and dendritic cells) have the potential to serve as clinically meaningful biomarkers of active MS2. Hence, there is a critical need for non-invasive molecular imaging strategies to accurately quantify and track myeloid cells and their functional phenotypes in MS patients. We previously identified triggering receptor expressed on myeloid cells 1 (TREM1) as a highly-specific marker of pro-inflammatory peripheral myeloid cells, developed the first TREM1-targeted positron emission tomography (PET) probe and demonstrated the ability of TREM1-PET to track CNS-infiltrating peripheral myeloid cells in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS3,4. Here, we investigate the ability of TREM1-PET to monitor active disease in the clinically relevant relapsing-remitting (RR-EAE) mouse model of MS. Additionally, we explore the potential of TREM1 as a clinical biomarker of active MS lesions via immunostaining of rare brain biopsy tissue. METHODS: Animals: SJL mice were induced with RR-EAE using PLP139-151 emulsified in immune adjuvant. Mice during active EAE disease (exhibiting paresis and/or paralysis) and remission (exhibiting complete recovery following initial EAE symptoms, similar to what occurs in RR-MS patients) were used for this study. Imaging: Anti-TREM1 monoclonal antibody (mAb) was DOTA-conjugated and radiolabeled with 64Cu. PET/CT imaging was performed 20 h post-injection of [64Cu]TREM1-mAb (95-120 μCi, >99% RCP). Following PET, mice were perfused with saline to remove any unbound intravascular tracer and spinal cords were analyzed via high-resolution autoradiography. Biopsy: Brain lesion from a drug and steroid naive tumefactive MS patient was characterized using standard immunostaining including Luxol Fast Blue and Myelin Basic Protein (demyelination), neurofilament and Bielschowsky’s Silver stain (axonal degeneration), H&E (general immune cells), CD3 (T cells) and CD20 (B cells). TREM1 staining was then performed on MS and control (non-MS) tissue. RESULTS: TREM1-PET images reveled significantly elevated signal in the spinal cords of RR-EAE mice during active disease compared to naive and EAE mice in remission (Fig. 1Ai). Ex vivo autoradiography images confirmed these findings (Fig. 1Aii). Quantification of PET images revealed markedly increased tracer binding in lumbar and thoracic spinal cords of diseased EAE versus naive mice (p<0.0001, Fig.1Bi-ii). Notably, the increased signal in diseased EAE was significantly reduced in EAE mice experiencing remission (p<0.0001). Increased TREM1-PET signal was also observed in the brains of EAE versus naive mice (p<0.05-p<0.0001, Fig. 1Biii-vi), with a significant decrease in signal in the whole brains and medulla of EAE remission mice (p<0.05). Immunostaining of MS brain biopsy tissue confirmed the presence of MS pathophysiology with significant demyelination, axonal degeneration and immune cell infiltration (Fig.2). Moreover, TREM1+ cells were identified in perivascular regions and TREM1 staining was substantially increased in MS compared to non-MS control tissue. CONCLUSION: TREM1-PET successfully discriminated active disease and remission in RR-EAE mice. Furthermore, this is the first report of the presence of TREM1+ cells in human MS brain. Thus, TREM1-PET has high potential for clinical impact on disease and therapeutic monitoring for individual RR-MS patients.

Recent grants

• Protective Prostaglandin Receptors in Cerebral Ischemia

  NIH · $3.7M · 2004–2017

Frequent coauthors

• Nathaniel S. Woodling

  University of Glasgow

  4 shared

• Xibin Liang

  Stanford University

  4 shared

• Jenny U. Johansson

  Stanford University

  3 shared

• Qian Wang

  Allen Institute for Brain Science

  3 shared

• Hidetoshi Taniguchi

  Izumi City General Hospital

  2 shared

• Michael R. Mancuso

  2 shared

• Junlei Chang

  Chinese Academy of Sciences

  2 shared

• Bereketeab Haileselassie

  Stanford University

  2 shared

Labs

• Andreasson LabPI

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