Alzheimer's Symposium: Spotlighting the Challenges and Advancements in Translational Work on Alzheimer's Disease Models

1. Ottavio Arancio (Professor of Pathology and Cell Biology and of Medicine, Columbia University, USA).
Dr Arancio is a cellular neurobiologist who has contributed to the characterization of the mechanisms of learning in both normal conditions and during neurodegenerative diseases. During the last ten years he has pioneered the field of mechanisms of synaptic dysfunction in Alzheimer’s disease. Dr. Arancio’s laboratory has focused primarily on events triggered by oligomeric proteins including amyloid-beta and tau. These studies have suggested new links between synaptic dysfunction and dementia, both for understanding the etiopathogenesis of Alzheimer’ disease and traumatic braininjury, and for developing therapies aiming to improve the cognitive symptoms. His representative publications: Nat Neurosci 2023 Aug;26(8):1365-1378; J Clin Invest.2020 Sep 1;130(9):4831-4844; Neuron. 2020 Nov 25;108(4):583-585; Nat Med. 2019 Jan;25(1):165-175

2. Claudio Grassi (President of Italian National Board of Full professors of Physiology, President, Cattolica-TJU Research s.r.l., Head of the Dept. of Neuroscience, Università Cattolica Medical School, Italy).
Prof. Grassi's scientific interests concern the following topics: mechanisms of regulation of brain plasticity and neuronal excitability in physiological conditions and in experimental models of neuropsychiatric diseases; molecular, electrophysiological and behavioral biomarkers of cognitive decline in experimental models of Alzheimer's disease; role of viral infections in the pathogenesis of neurodegenerative diseases; effects of non-invasive brain stimulation on brain plasticity; impact of cerebral insulin resistance on synaptic plasticity and cognitive functions; mechanisms regulating the proliferation and differentiation of neural stem cells and adult neurogenesis; Mechanisms responsible for cochlear damage and their impact on the plasticity of theauditory cortex. His representative publications: Sci Adv. 2023 Nov 17;9(46); Transl Neurodegener. 2022 Nov 27;11(1):50; Elife. 2021 Oct 26;10:e70908.

3. Giulio Taglialatela (Director of UTMB Brain Health Institute, Del Papa Distinguished Chair in Neurodegenerative Diseases, Director of Mitchell Center for Neurodegenerative Diseases, Professor and Vice Chair, Dept of Neurology UTMB Galveston, University ofTexas, USA).
Dr. Taglialatela’s research focuses on the molecular neurobiology of Alzheimer’s disease and related neurodegenerative disorders attracting support from the NIH, the State of Texas and multiple foundations. He has published over 100 peer-reviewed papers and delivered invited talks nationally and internationally. Dr. Taglialatela has served on national and international grant review panels. His representative publications: Acta Neuropathol. 2023 Mar;145(3):303-324; Brain Pathol. 2023 Jan;33(1):e13108; Alzheimers Dement. 2023 Dec;19(12):5355-5370.

4. Andre Fischer (Professor, Dep. for Systems Medicine an Epigenetics, German Center for Neurodegenerative Disease (DZNE), University Medical Center Göttingen, Germany).
The long-term goal of Dr. Fischer’s major research focus is to understand the pathogenesis of Alzheimer’s disease (AD) and to identify effective therapeutic strategies. Their current hypothesis is that deregulation of genome-environment interactions, especially via epigenetic gene-expression, is a key feature of neurodegenerative diseases such as Alzheimer’s disease. Their aim is to define combinatorial maps of epigenetic-modifications during disease progression and therapeutic intervention. The data will be combined with the analysis of the corresponding key-enzymes of epigenetic gene-expression. Their mechanistic approaches involve genetic and pharmacological means to investigate how individual chromatin-modifying enzymes affect neuronal plasticity, synaptic function and learning & memory in the young, aging and diseased brain. His representative publications: The New England journal of medicine 2023; 388(19), 1816 –1817; PNAS 2023; 120(9), e2204933120; The EMBO journal 2022; 41(1)

5. Charalampos (Haris) Tzoulis (co-director of the Neuro-SysMed Center of Excellence forClinical Research in Neurological diseases, UiB, Norway).
Prof. Tzoulis is an expert on movement disorders and neurodegeneration, including dementia and parkisonism. His research focuses on exploring the role of mitochondrial dysfunction in Parkinson's disease (PD) with the aim to improve patient diagnosis and develop neuroprotective therapies. He is the Principal Investigator of the research group Neuromics at the University of Bergen and co-Director of the Neuro-SysMed Center of Excellence for Clinical Research in Neurological diseases. Since 2022, he is also the Director of the K.G. Jebsen Center for Translational Research in Parkinson's Disease at UiB. His representative publications: Nat Commun. 2023 Nov 28;14(1):7793; Genome Med. 2023 Jun 7;15(1):41; Cell Metab. 2022 Mar 1;34(3):396-407.

6. Asgeir Kobro-Flatmoen (co-coordinator of the Norwegian National Anti-Alzheimer’s disease (No-AD) Network, co-leader of K.G.Jebsen Centre for Alzheimer´s Disease, Kavli institute in Trondheim, Norway).
Dr. Kobro-Flatmoen does research on the neuroanatomy and cell-biology of Alzheimer’s disease, and has discovered the unique vulnerability for a specific subset of neurons in entorhinal cortex layer II to the accumulation of amyloid-beta, namely the reelin-expressingprojection neurons. His current work is centered on understanding how processes in these neurons may set off the disease-cascade. His representative publications: J Alzheimers Dis. 2023;95(2):719-733; Brain Commun. 2023 Apr 6;5(2):fcad115; J Neurosci Methods. 2023 Apr 15;390:109840; Neurobiol Dis. 2016 doi 10.1016/j.nbd.2016.05.012.

7. Kei Cho (professor, Kings College London, UK).
Kei Cho is an expert in synaptic plasticity in Alzheimer’s disease (AD). As an Affiliated PIat the UK DRI at Kings he leads an innovative research program investigating synapseweakeningin AD. In 2011 he was awarded the Wolfson Research Merit Award of theRoyal Society, was Vice-President of the London Health Forum in 2013, and co-foundedthe UK-Korea Neuroscience Consortium. His representative publications: ActaNeuropathol Commun. 2023 Dec 18;11(1):199; Brain Commun. 2022 Apr 8;4(2):fcac083;J Neurosci. 2021 Aug 25;41(34):7162-7170.

8. Juan Song (Jeffrey Houpt Distinguished Investigator, professor, University of North Carolina, USA).
The overarching goals of Dr. Song’s research are: 1) To understand how the healthy adult brain regenerates from endogenous neural stem cells and apply basic learned principles to the degenerated brain to promote regeneration; 2) To investigate how circuit- and behavior-level information-processing properties are remodeled by the integration of new neurons into the existing circuits; 3) To explore the circuit and signaling mechanisms regulating hippocampal-dependent memory and emotion processing in health and Alzheimer’s disease. Her representative publications: Cell Stem Cell 2023. 30(4), 415-432; Nature Neuroscience 2022. 25(5):630-645; Neuron 2020.108(2):349-366.

9. Hongyu ZHANG, MD, PhD, organizer and chair of the symposium (Researcher, UiB, Norway).
Dr. Zhang's research is centered on developing tools for modulating AMPA receptor synaptic anchoring, with a focus on their application to reverse memory deficits associated with neurodegenerative and psychiatric disorders. In 2023, she was awarded one innovation grant from Helse Vest and two from UiB IDE to support the development of small interfering peptides. These peptides are aimed at treating depression and slowing the progression of Alzheimer’s disease. Her representative publications: Nat Commun. 2018 Oct 15;9(1):4272; J Clin Invest 2016 Feb;126(2):627-38; Mol Psychiatry. 2013 Apr;18(4):471-84.

10. Elena De Cecco (Institute of Neuropathology, University Hospital Zurich and UZH).
Dr. De Cecco is a postdoctoral researcher working in the laboratory of Prof. Adriano Aguzzi, who has pioneered the field of prion diseases for more than 30 years. Combining transgenetics with cutting-edge molecular biology, Prof. Aguzzi’s laboratory has described all key events leading to prion neuroinvasion, spreading and toxicity. In the last 5 years, his group generated two genome-wide arrayed human CRISPR libraries and is currently expanding his research interests in the fields of synucleinopathies and lysosomal storage disorders. Dr. De Cecco focuses on understanding the molecular pathways driving the progression of neurodegenerative proteinopathies. By exploiting CRISPR-based forward genetics, she investigates the mechanisms by which prions and a-synuclein aggregates infect cells and self-replicate to propagate the pathology. Representative publications: Yin et al., 2022, bioRxiv (submitted to Nature Biomedical Engineering); Frontzek et al., 2022, Nature Structural and Molecular Biology; De Cecco et al., 2020, J. Neurochemistry.

11. Maria-Adelaide Micci (Professor, Dept of Neurology UTMB Galveston, University ofTexas, USA).
Dr. Micci's current research primarily centers on neurogenesis, with a focus on investigating how hippocampal neural stem cells can enhance synaptic resilience against toxic amyloid oligomers through secreted exosomes, and on developing non-invasive transcranial nano-pulsed laser therapy for treating brain injury and neurodegenerative disorders. Her research has received funding from the NIH, the DoD, and private foundations. She has been invited to speak at national and international conferences and serves on grant review panels for the NIH. Her representative publications: Mol Neurodegener. 2019 Jun 14;14(1):25.; J Neurotrauma. 2018 Jul 1;35(13):1510-1522; J Neurotrauma 2020 Apr 15;37(8):1108-1123”

12. Bai Lu (Professor in the School of Pharmaceutical Sciences at Tsinghua University).
Dr. Lu pioneered research in the role of neurotrophins in synapse development and plasticity, and is credited for several major discoveries: 1) discovery of BDNF regulation of LTP, a cellular model for memory; 2) identification of a SNP that impacts BDNF secretion and short-term memory in human; 3) elucidation extracellular cleavage of proBDNF to mature BDNF and its role in long-term synaptic plasticity; 4) demonstration of the opposing roles of proBDNF and mature BDNF in synaptic plasticity, leading to a "Yin-Yang" hypothesis of neurotrophin actions; 5) revealing the functional role of activity-dependentBDNF transcription; 6）discovery of proBDNF to mature BDNF conversion in activity-dependent competition at developing neuromuscular synapses; 7) raising the therapeutic strategy of "BDNF-based synaptic repair" for neurodegenerative diseases. Dr. Lu has recently developed a knock-in rat model for Alzheimer’s disease. His representative publications are as follows: Cell Res. 2022 Feb;32(2) 157-175; Nat Commun. 2022 Feb 17;13(1):914.

13. Takaomi C. Saido (Professor, RIKEN Center for Brain Science, Wako, Japan).
Dr. Saido's primary interests revolve around identifying and utilizing Aβ-degrading enzymes and developing relevant animal models that do not rely on an overexpression paradigm for preclinical AD treatment. He and his colleagues made significant discoveries in this field, including the identification of neprilysin (neutral endopeptidase) as a major in vivo Aβ-degrading enzyme (Iwata et al., Nat Med, 2000; Science 2001). Their research efforts focused on targeting neprilysin, leading to the discovery that the binding of somatostatin to a somatostatin receptor heterodimer composed of subtypes 1 and 4selectively enhances neprilysin expression and activity (Saito et al., Nat Med, 2005; Saido et al., Japanese Patent 7099717, 2022). Additionally, Dr. Saido's laboratory developed the world's first single App knock-in mouse models, which replicate AD pathology without relying on an overexpression paradigm (Saito et al., Nat Neurosci, 2014). These models have been adopted by over 800 research groups worldwide (Saido, Alzheimer's Disease Research Guide (Elsevier Inc), 2024). Due to his groundbreaking work, Dr. Saido has become one of the most highly cited scientists in the research community.

14. Henriette Aksnes (Group leader at the Department of Biomedicine, UiB, Norway; co-leadof the Bergen node in the Norwegian light microscopy network NALMIN).
Dr. Aksnes is a molecular cell biologist with expertise on modification of membrane proteins. Via translational protein research, Aksnes’ interests span a variation of neurodegenerative diseases as well as normal neurobiology. Her previous basal research recently gained impact as the membrane protein modifier NAA60 was connected to primary familial brain calcification (PFBC). Aksnes was awarded the Meltzer award for young researchers in 2022 and a starting grant from the Trond Mohn Research Foundation 2023. Her lab will further explore the role of N-terminal acetylation in neurodegenerative disease and neurobiology. Her representative publications: Nat Commun. 2024 Mar 13;15(1):2269; J Cell Sci. 2023 Jul 15;136(14); Exp Cell Res. 2020 May 15;390(2):111961; Proc Natl Acad Sci U S A. 2018 Apr 24;115(17):4399-4404.

15. Xiangning Li (Professor at Hainan University, China).
Xiangning Li’s research goal is to understand the organizational logic of neural system and the pathophysiological mechanisms of neurological disorders. He developed a series of sample preparation techniques to maintain the fluorescent signals in the large-volume biological tissues. He acquired the whole-brain datasets the neuronal circuits, including the morphological and synaptic information during ageing and degenerative diseases. His representative publications: Nature Neuroscience, 2019, 22:1357-1370; Nat Commun, 2022, 13 (1): 998; and PNAS, 2022, 119(40):e2202536119.

Sunday 2 June, 2024

10:00 – 10:15 Welcome remarks

10:15 – 10:45 Giulio Taglialatela (University of Texas, USA)

Topic: Promoting cognitive resilience in the face of Alzheimer’s neuropathology: a noveltherapeutic venue

10:45 – 11:15 Charalampos (Haris) Tzoulis (UiB, Norway)

Topic: NAD+ in Brain Aging and Neurodegenerative Disorders

11:15 – 11:30 Coffee Break

11:30 – 12:00 Kei Cho (Kings College London, UK)

Topic: Emerging insights into synapse dysregulation in Alzheimer's disease

12:00 – 12:30 Hongyu Zhang (University of Bergen, Norway)

Topic: An interfering peptide to slow the progression of Alzheimer’s disease

12:30-13:30 Lunch

13:30 – 14:00 Ottavio Arancio (Columbia University, USA)

Topic: Dysregulation of synaptic vesicle release by aβ and tau oligomers

14:00-14:30 Asgeir Kobro-Flatmoen (Kavli institute in Trondheim, Norway) Via Zoom

Topic: Altered Proteins and the histopathology Behind Entorhinal Cortex Dysfunction in Alzheimer’s disease

14:30 – 15:00 Henriette Aksnes (University of Bergen, Norway)

Topic: New genetic insight to brain calcification

15:00 – 15:15 Coffee break

15:15 – 15:45 Takaomi C. Saido (Professor, RIKEN Center for Brain Science, Wako, Japan)

Topic: Creation of next-generation animal models of FTDP-17 and AD that exhibit Aβ-independentand -dependent tau pathology without depending on an overexpression paradigm

15:45 – 16:15 Bai Lu (Tsinghua University, China)

Topic: An App knock-in rat model for Alzheimer's disease exhibiting Aβ and tau pathologies, neuronal death and cognitive impairments

16:15 – 17: 30 Debate: What are the caveats for the current hypothesis for Alzheimer’s disease? What are the advantages and disadvantages of different AD models ?

17:30 – 19:00 Leisure time

19:00 – 21:00 Dinner

Monday 3 June, 2024

8:30 – 9:00 Elena De Decco (representing the laboratory of Prof. Adriano Aguzzi)

Topic: Investigating the life cycle of prions with forward genetics

9:00 – 9:30 Andre Fischer (University Medical Center Göttingen, Germany) Via Zoom

Topic: The non-coding RNAome as a target for stratified therapies in Neurodegenerative Diseases

9:30 – 10:00 Juan Song (University of North Carolina, USA) Via Zoom

Topic: Activation of hypothalamic-enhanced adult-born neurons restores cognitive and affective function in Alzheimer’s disease

10:00 – 10:15 Coffee break

10:15 – 10:45 Maria-Adelaide Micci

Topic: ‘Looking beyond neurogenesis: The impact of neural stem cells on the brain in the context of Alzheimer’s disease’

10:45 – 11:15 Xiangning Li (Professor, Hainan University, China) Via Zoom

Topic: Mesoscopic dissection of neural circuit in Alzheimer's disease

11:15 – 11:45 Claudio Grassi (Università Cattolica, Italy)

Topic: Role of neuron-glial cell crosstalk in the synaptic and memory deficits of Alzheimer's mouse models

11:45 – 12:55 What are the possible avenues towards the treatment of Alzheimer's disease?
How can participants effectively forge collaborations?

12:55 – 13:00 Concluding remarks

13:00 – 14:30 Lunch and departure