{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T05:07:23Z","timestamp":1780636043660,"version":"3.54.1"},"reference-count":89,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:00:00Z","timestamp":1780617600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:p>Metabolic dysregulation is increasingly being recognized as a hallmark across various neurodegenerative diseases. While Alzheimer\u2019s disease (AD) is well-established as a dual proteinopathy characterized by amyloid-beta (A\u03b2) deposition and tau protein tangles, the specific mechanisms mediating lipid homeostasis imbalance have garnered increasing attention. However, translating these findings into safe clinical therapeutic targets remains a formidable challenge, primarily hindered by the pleiotropic roles of ceramides in maintaining neural and immune homeostasis, as well as the blood\u2013brain barrier (BBB) penetration issues and systemic safety limitations of current sphingolipid-targeting strategies. We conducted a comprehensive search of electronic databases, including PubMed, Web of Science, and Google Scholar, to identify relevant studies published from database inception through March 2026. The search term combinations included: \u201cAlzheimer\u2019s disease,\u201d \u201cAD,\u201d \u201cceramide,\u201d \u201csphingolipid metabolism,\u201d \u201cbiomarker,\u201d \u201ctherapeutic target,\u201d \u201cneuroinflammation,\u201d and \u201cmitochondrial dysfunction.\u201d To ensure the depth and rigor of this review, priority was given to peer-reviewed original research, systematic reviews, and meta-analyses. The search was restricted to English-language literature. Additionally, the reference lists of retrieved articles were manually screened to identify further relevant studies. This narrative review aims to comprehensively elucidate the potential roles of ceramides in AD pathogenesis, exploring their associations with triggering inflammatory responses, mediating apoptosis, interfering with signal transduction, and inducing mitochondrial dysfunction.<\/jats:p>","DOI":"10.3389\/fnins.2026.1771302","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T04:53:58Z","timestamp":1780635238000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring ceramide as a novel biomarker and therapeutic target for Alzheimer\u2019s disease"],"prefix":"10.3389","volume":"20","author":[{"given":"Wangting","family":"Zhao","sequence":"first","affiliation":[{"name":"The FirstAffiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Liu","sequence":"additional","affiliation":[{"name":"The FirstAffiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yimin","family":"Yao","sequence":"additional","affiliation":[{"name":"The FirstAffiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Yu","sequence":"additional","affiliation":[{"name":"The FirstAffiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengjun","family":"Hu","sequence":"additional","affiliation":[{"name":"The FirstAffiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,5]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1016\/S0197-4580(00)00126-3","article-title":"Morphological and biochemical assessment of DNA damage and apoptosis in down syndrome and Alzheimer disease, and effect of postmortem tissue archival on TUNEL","volume":"21","author":"Anderson","year":"2000","journal-title":"Neurobiol. 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