TY  - JOUR
AU  - Vergallo, Andrea
AU  - Caraci, Filippo
AU  - Cuello, A Claudio
AU  - Lemercier, Pablo
AU  - Vellas, Bruno
AU  - Giudici, Kelly Virecoulon
AU  - Hampel, Harald
AU  - Baldacci, Filippo
AU  - Hänisch, Britta
AU  - Haberkamp, Marion
AU  - Broich, Karl
AU  - Nisticò, Robert
AU  - Emanuele, Enzo
AU  - Llavero, Francisco
AU  - Zugaza, José L
AU  - Lucía, Alejandro
AU  - Giacobini, Ezio
AU  - Lista, Simone
TI  - Future avenues for Alzheimer's disease detection and therapy: liquid biopsy, intracellular signaling modulation, systems pharmacology drug discovery.
JO  - Neuropharmacology
VL  - 185
SN  - 0028-3908
CY  - Amsterdam [u.a.]
PB  - Elsevier Science
M1  - DZNE-2021-01080
SP  - 108081
PY  - 2021
AB  - 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</td><td width="150">
AB  - 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'.
KW  - Alzheimer Disease: diagnosis
KW  - Alzheimer Disease: drug therapy
KW  - Alzheimer Disease: metabolism
KW  - Animals
KW  - Anti-Inflammatory Agents: administration & dosage
KW  - Anti-Inflammatory Agents: metabolism
KW  - Drug Discovery: methods
KW  - Drug Discovery: trends
KW  - Drug Repositioning: methods
KW  - Drug Repositioning: trends
KW  - Forecasting
KW  - Humans
KW  - Intracellular Fluid: drug effects
KW  - Intracellular Fluid: metabolism
KW  - Liquid Biopsy: methods
KW  - Liquid Biopsy: trends
KW  - Membrane Glycoproteins: metabolism
KW  - Pharmacology, Clinical: methods
KW  - Pharmacology, Clinical: trends
KW  - Receptors, Immunologic: metabolism
KW  - Signal Transduction: drug effects
KW  - Signal Transduction: physiology
KW  - Systems Biology: methods
KW  - Systems Biology: trends
KW  - Alzheimer's disease (Other)
KW  - Blood biomarkers (Other)
KW  - Disease-modifying therapies (Other)
KW  - Liquid biopsy (Other)
KW  - Precision medicine (Other)
KW  - Systems pharmacology (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:32407924
DO  - DOI:10.1016/j.neuropharm.2020.108081
UR  - https://pub.dzne.de/record/155926
ER  -