Frontotemporal Lobar Degeneration

NOMIS Project 2016

— 2022

The German Center for Neurodegenerative Diseases (Deutsches Zentrum für Neurodegenerative Erkrankungen, DZNE) is committed to understanding commonalities and differences between various brain diseases in order to develop new preventive and therapeutic approaches. The Frontotemporal Lobar Degeneration – from the Basic Mechanism and Target Identification to Translational and Clinical Approaches project is based on a new, cross-cutting approach: clinical and basic research are done at the same time, which allows their results to be directly fed into each other’s processes. NOMIS is supporting this innovative framework by matching DZNE funding for the clinical research with funding for the basic research component; this will focus on identifying therapeutic targets and understanding their physiological function, as well as finding the mechanism through which mutant genes cause the disease. The Frontotemporal Lobar Degeneration project comprises the search for biomarkers as well as screening for disease-modulating compounds.

The project is being led by Christian Haass and Dieter Edbauer at the DZNE.

Christian Haass

Member of the NOMIS Foundation Board of Directors

German Center for Neurodegenerative Diseases (DZNE), NOMIS Foundation

Dieter Edbauer

Professor

Ludwig-Maximilians-Universität München

February 8, 2023

Christian Haass awarded Hector Wissenschaftspreis 2022

NOMIS Board Member and researcher Christian Haass has been awarded the 2022 Hector Wissenschaftspreis (science award) for his groundbreaking research on Alzheimer’s disease, his interdisciplinary approach as a university professor, […]

September 16, 2023

Phenylalanine-tRNA aminoacylation is compromised by ALS/FTD-associated C9orf72 C4G2 repeat RNA

Abstract: The expanded hexanucleotide GGGGCC repeat mutation in the C9orf72 gene is the main genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. Under one disease mechanism, sense and antisense transcripts of the repeat are predicted to bind various RNA-binding proteins, compromise their function and cause cytotoxicity. Here we identify phenylalanine-tRNA

DOI: 10.1038/s41467-023-41511-3

September 14, 2023

Additive value of [18F]PI-2620 perfusion imaging in progressive supranuclear palsy and corticobasal syndrome

Abstract: Purpose: Early after [18F]PI-2620 PET tracer administration, perfusion imaging has potential for regional assessment of neuronal injury in neurodegenerative diseases. This is while standard late-phase [18F]PI-2620 tau-PET is able to discriminate the 4-repeat tauopathies progressive supranuclear palsy and corticobasal syndrome (4RTs) from disease controls and healthy controls. Here, we investigated

DOI: 10.1007/s00259-022-05964-w

August 17, 2023

Distinct molecular profiles of skull bone marrow in health and neurological disorders

Abstract: The bone marrow in the skull is important for shaping immune responses in the brain and meninges, but its molecular makeup among bones and relevance in human diseases remain unclear. Here, we show that the mouse skull has the most distinct transcriptomic profile compared with other bones in states of

DOI: 10.1016/j.cell.2023.07.009

June 29, 2023

Psychotic symptoms in frontotemporal dementia with TDP-43 tend to be associated with type B pathology

Abstract: Aims: Psychotic symptoms are increasingly recognized as a distinguishing clinical feature in patients with dementia due to frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP). Within this group, carriers of the C9orf72 repeat expansion are particularly prone to develop delusions and hallucinations. Methods: The present retrospective study sought to provide novel

DOI: 10.1111/nan.12921

May 9, 2023

Live Cell Imaging of ATP Levels Reveals Metabolic Compartmentalization within Motoneurons and Early Metabolic Changes in FUS ALS Motoneurons

Abstract: Motoneurons are one of the most energy-demanding cell types and a primary target in Amyotrophic lateral sclerosis (ALS), a debilitating and lethal neurodegenerative disorder without currently available effective treatments. Disruption of mitochondrial ultrastructure, transport, and metabolism is a commonly reported phenotype in ALS models and can critically affect survival and

DOI: 10.3390/cells12101352

February 15, 2023

Systematic estimation of biological age of in vitro cell culture systems by an age-associated marker panel

Abstract: Aging is a process that affects almost all multicellular organisms and since our population ages with increasing prevalence of age-related diseases, it is important to study basic processes involved in aging. Many studies have been published so far using different and often single age markers to estimate the biological age

DOI: 10.3389/fragi.2023.1129107

January 24, 2023

FUS ALS neurons activate major stress pathways and reduce translation as an early protective mechanism against neurodegeneration

Abstract: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder causing progressive loss of motor neurons. Mutations in Fused in sarcoma (FUS) leading to its cytoplasmic mislocalization cause a subset of ALS. Under stress, mutant FUS localizes to stress granules (SGs)—cytoplasmic condensates composed of RNA and various proteins. Aberrant dynamics of SGs

DOI: 10.1016/j.celrep.2023.112025

December 13, 2022

LATE-NC staging in routine neuropathologic diagnosis: an update

Abstract: An international consensus report in 2019 recommended a classification system for limbic-predominant age-related TDP-43 encephalopathy neuropathologic changes (LATE-NC). The suggested neuropathologic staging system and nomenclature have proven useful for autopsy practice and dementia research. However, some issues remain unresolved, such as cases with unusual features that do not fit with

DOI: 10.1007/s00401-022-02524-2