{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T18:33:45Z","timestamp":1792175625484,"version":"4.4.0"},"reference-count":272,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,12]],"date-time":"2022-11-12T00:00:00Z","timestamp":1668211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is the most frequent case of neurodegenerative disease and is becoming a major public health problem all over the world. Many therapeutic strategies have been explored for several decades; however, there is still no curative treatment, and the priority remains prevention. In this review, we present an update on the clinical and physiological phase of the AD spectrum, modifiable and non-modifiable risk factors for AD treatment with a focus on prevention strategies, then research models used in AD, followed by a discussion of treatment limitations. The prevention methods can significantly slow AD evolution and are currently the best strategy possible before the advanced stages of the disease. Indeed, current drug treatments have only symptomatic effects, and disease-modifying treatments are not yet available. Drug delivery to the central nervous system remains a complex process and represents a challenge for developing therapeutic and preventive strategies. Studies are underway to test new techniques to facilitate the bioavailability of molecules to the brain. After a deep study of the literature, we find the use of soft nanoparticles, in particular nanoliposomes and exosomes, as an innovative approach for preventive and therapeutic strategies in reducing the risk of AD and solving problems of brain bioavailability. Studies show the promising role of nanoliposomes and exosomes as smart drug delivery systems able to penetrate the blood\u2013brain barrier and target brain tissues. Finally, the different drug administration techniques for neurological disorders are discussed. One of the promising therapeutic methods is the intranasal administration strategy which should be used for preclinical and clinical studies of neurodegenerative diseases.<\/jats:p>","DOI":"10.3390\/ijms232213954","type":"journal-article","created":{"date-parts":[[2022,11,14]],"date-time":"2022-11-14T02:29:32Z","timestamp":1668392972000},"page":"13954","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":596,"title":["Alzheimer\u2019s Disease: Treatment Strategies and Their Limitations"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2908-2359","authenticated-orcid":false,"given":"Elodie","family":"Passeri","sequence":"first","affiliation":[{"name":"LIBio Laboratory, University of Lorraine, 54505 Vandoeuvre-l\u00e8s-Nancy, France"},{"name":"UR AFPA Laboratory, Qualivie Team, University of Lorraine, 54505 Vandoeuvre-l\u00e8s-Nancy, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8160-9333","authenticated-orcid":false,"given":"Kamil","family":"Elkhoury","sequence":"additional","affiliation":[{"name":"LIBio Laboratory, University of Lorraine, 54505 Vandoeuvre-l\u00e8s-Nancy, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5511-6105","authenticated-orcid":false,"given":"Margaretha","family":"Morsink","sequence":"additional","affiliation":[{"name":"Department of Applied Stem Cell Technologies, TechMed Centre, University of Twente, 7500AE Enschede, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerensa","family":"Broersen","sequence":"additional","affiliation":[{"name":"Department of Applied Stem Cell Technologies, TechMed Centre, University of Twente, 7500AE Enschede, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8658-6828","authenticated-orcid":false,"given":"Michel","family":"Linder","sequence":"additional","affiliation":[{"name":"LIBio Laboratory, University of Lorraine, 54505 Vandoeuvre-l\u00e8s-Nancy, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Tamayol","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Connecticut Health Center, Farmington, CT 06030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Malaplate","sequence":"additional","affiliation":[{"name":"UR AFPA Laboratory, Qualivie Team, University of Lorraine, 54505 Vandoeuvre-l\u00e8s-Nancy, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8740-4304","authenticated-orcid":false,"given":"Frances T.","family":"Yen","sequence":"additional","affiliation":[{"name":"UR AFPA Laboratory, Qualivie Team, University of Lorraine, 54505 Vandoeuvre-l\u00e8s-Nancy, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elmira","family":"Arab-Tehrany","sequence":"additional","affiliation":[{"name":"LIBio Laboratory, University of Lorraine, 54505 Vandoeuvre-l\u00e8s-Nancy, France"},{"name":"Department of Biomedical Engineering, University of Connecticut Health Center, Farmington, CT 06030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/S0140-6736(15)01124-1","article-title":"Alzheimer\u2019s Disease","volume":"388","author":"Scheltens","year":"2016","journal-title":"Lancet"},{"key":"ref_2","unstructured":"Prince, M.J. 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