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@ARTICLE{Vergallo:155926,
      author       = {Vergallo, Andrea and Caraci, Filippo and Cuello, A Claudio
                      and Lemercier, Pablo and Vellas, Bruno and Giudici, Kelly
                      Virecoulon and Hampel, Harald and Baldacci, Filippo and
                      Hänisch, Britta and Haberkamp, Marion and Broich, Karl and
                      Nisticò, Robert and Emanuele, Enzo and Llavero, Francisco
                      and Zugaza, José L and Lucía, Alejandro and Giacobini,
                      Ezio and Lista, Simone},
      collaboration = {Initiative, Alzheimer Precision Medicine},
      title        = {{F}uture avenues for {A}lzheimer's disease detection and
                      therapy: liquid biopsy, intracellular signaling modulation,
                      systems pharmacology drug discovery.},
      journal      = {Neuropharmacology},
      volume       = {185},
      issn         = {0028-3908},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier Science},
      reportid     = {DZNE-2021-01080},
      pages        = {108081},
      year         = {2021},
      abstract     = {When Alzheimer's disease (AD) disease-modifying therapies
                      will be available, global healthcare systems will be
                      challenged by a large-scale demand for clinical and
                      biological screening. Validation and qualification of
                      globally accessible, minimally-invasive, and time-,
                      cost-saving blood-based biomarkers need to be advanced.
                      Novel pathophysiological mechanisms (and related candidate
                      biomarkers) - including neuroinflammation pathways (TREM2
                      and YKL-40), axonal degeneration (neurofilament light chain
                      protein), synaptic dysfunction (neurogranin, synaptotagmin,
                      α-synuclein, and SNAP-25) - may be integrated into an
                      expanding pathophysiological and biomarker matrix and,
                      ultimately, integrated into a comprehensive blood-based
                      liquid biopsy, aligned with the evolving
                      ATN + classification system and the precision medicine
                      paradigm. Liquid biopsy-based diagnostic and therapeutic
                      algorithms are increasingly employed in Oncology
                      disease-modifying therapies and medical practice, showing an
                      enormous potential for AD and other brain diseases as well.
                      For AD and other neurodegenerative diseases, newly
                      identified aberrant molecular pathways have been identified
                      as suitable therapeutic targets and are currently
                      investigated by academia/industry-led $R\&D$ programs,
                      including the nerve-growth factor pathway in basal forebrain
                      cholinergic neurons, the sigma1 receptor, and the GTPases of
                      the Rho family. Evidence for a clinical long-term effect on
                      cognitive function and brain health span of cholinergic
                      compounds, drug candidates for repositioning programs, and
                      non-pharmacological multidomain interventions (nutrition,
                      cognitive training, and physical activity) is developing as
                      well. Ultimately, novel pharmacological paradigms, such as
                      quantitative systems pharmacology-based
                      integrative/explorative approaches, are gaining momentum to
                      optimize drug discovery and accomplish effective
                      pathway-based strategies for precision medicine. This
                      article is part of the special issue on 'The Quest for
                      Disease-Modifying Therapies for Neurodegenerative
                      Disorders'.},
      subtyp        = {Review Article},
      keywords     = {Alzheimer Disease: diagnosis / Alzheimer Disease: drug
                      therapy / Alzheimer Disease: metabolism / Animals /
                      Anti-Inflammatory Agents: administration $\&$ dosage /
                      Anti-Inflammatory Agents: metabolism / Drug Discovery:
                      methods / Drug Discovery: trends / Drug Repositioning:
                      methods / Drug Repositioning: trends / Forecasting / Humans
                      / Intracellular Fluid: drug effects / Intracellular Fluid:
                      metabolism / Liquid Biopsy: methods / Liquid Biopsy: trends
                      / Membrane Glycoproteins: metabolism / Pharmacology,
                      Clinical: methods / Pharmacology, Clinical: trends /
                      Receptors, Immunologic: metabolism / Signal Transduction:
                      drug effects / Signal Transduction: physiology / Systems
                      Biology: methods / Systems Biology: trends / Alzheimer's
                      disease (Other) / Blood biomarkers (Other) /
                      Disease-modifying therapies (Other) / Liquid biopsy (Other)
                      / Precision medicine (Other) / Systems pharmacology (Other)},
      cin          = {AG Hänisch},
      ddc          = {610},
      cid          = {I:(DE-2719)1013010},
      pnm          = {354 - Disease Prevention and Healthy Aging (POF4-354)},
      pid          = {G:(DE-HGF)POF4-354},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:32407924},
      doi          = {10.1016/j.neuropharm.2020.108081},
      url          = {https://pub.dzne.de/record/155926},
}