{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T03:01:18Z","timestamp":1785466878881,"version":"3.56.0"},"reference-count":155,"publisher":"SAGE Publications","issue":"s1","license":[{"start":{"date-parts":[[2021,6,22]],"date-time":"2021-06-22T00:00:00Z","timestamp":1624320000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2021,6,22]]},"abstract":"<jats:p>To deeply understand late onset Alzheimer\u2019s disease (LOAD), it may be necessary to change the concept that it is a disease exclusively driven by aging processes. The onset of LOAD could be associated with a previous peripheral stress at the level of the gut (changes in the gut microbiota), obesity (metabolic stress), and infections, among other systemic\/environmental stressors. The onset of LOAD, then, may result from the generation of mild peripheral inflammatory processes involving cytokine production associated with peripheral stressors that in a second step enter the brain and spread out the process causing a neuroinflammatory brain disease. This hypothesis could explain the potential efficacy of Sodium Oligomannate (GV\u2013971), a mixture of acidic linear oligosaccharides that have shown to remodel gut microbiota and slowdown LOAD. However, regardless of the origin of the disease, the end goal of LOAD\u2013related preventative or disease modifying therapies is to preserve dendritic spines and synaptic plasticity that underlay and support healthy cognition. Here we discuss how systemic\/environmental stressors impact pathways associated with the regulation of spine morphogenesis and synaptic maintenance, including insulin receptor and the brain derived neurotrophic factor signaling. Spine structure remodeling is a plausible mechanism to maintain synapses and provide cognitive resilience in LOAD patients. Importantly, we also propose a combination of drugs targeting such stressors that may be able to modify the course of LOAD by acting on preventing dendritic spines and synapsis loss.<\/jats:p>","DOI":"10.3233\/jad-201106","type":"journal-article","created":{"date-parts":[[2020,12,8]],"date-time":"2020-12-08T23:28:00Z","timestamp":1607470080000},"page":"S91-S107","source":"Crossref","is-referenced-by-count":21,"title":["Pharmacological Strategies to Improve Dendritic Spines in Alzheimer\u2019s Disease"],"prefix":"10.1177","volume":"82","author":[{"given":"Miren","family":"Ettcheto","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Science, University of Barcelona, Barcelona, Spain"},{"name":"Department of Biochemistry and Biotechnology, Faculty of Medicine and Life Science, University Rovira i Virgili, Reus, Spain"},{"name":"Biomedical Research Networking Centre in Neurodegenerative Diseases 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