{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T11:03:19Z","timestamp":1779706999240,"version":"3.53.1"},"reference-count":94,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"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. Nutr."],"abstract":"<jats:p>\n                    Intermittent fasting (IF) promotes a metabolic switch characterized by reduced glucose and insulin availability along with increased lipolysis and ketone body production, particularly\n                    <jats:italic>\u03b2<\/jats:italic>\n                    -hydroxybutyrate (\u03b2OHB). In the brain, IF enhances metabolic flexibility by facilitating ketone utilization and supporting the astrocyte\u2013neuron lactate shuttle (ANLS), partially compensating for cerebral glucose hypometabolism which is commonly observed in Alzheimer\u2019s disease (AD). Beyond bioenergetics, IF activates autophagy and inhibits mTOR signaling, promoting protein clearance and cellular homeostasis. Neuroinflammation is also attenuated with IF through the modulation of microglial activation. IF further induces increased levels of brain-derived neurotrophic factor (BDNF), thereby supporting synaptic plasticity and neuronal resilience. At the systemic level, IF enhances brain-peripheral crosstalk by improving adipose tissue function (e.g., leptin sensitivity and adipokine balance) and stimulating skeletal muscle\u2013derived myokine signaling, which collectively influence brain metabolism and inflammation. These integrated mechanisms converge to reduce amyloid-\u03b2 accumulation, tau pathology, and neuroinflammation, ultimately improving synaptic function and cognitive outcomes, as evidenced by preclinical rodent models and emerging clinical studies.\n                  <\/jats:p>","DOI":"10.3389\/fnut.2026.1839995","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T10:16:02Z","timestamp":1779704162000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Intermittent fasting and neuroprotection in Alzheimer\u2019s disease: metabolic mechanisms, cellular signaling, and brain-peripheral crosstalk"],"prefix":"10.3389","volume":"13","author":[{"given":"Keshari H.","family":"Sudasinghe","sequence":"first","affiliation":[{"name":"Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University","place":["Manhattan, KS, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie E.","family":"Hall","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University","place":["Manhattan, KS, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,25]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1002\/oby.22065","article-title":"Flipping the metabolic switch: understanding and applying the health benefits of fasting","volume":"26","author":"Anton","year":"2018","journal-title":"Obesity"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1210\/clinem\/dgaa644","article-title":"Intermittent fasting improves Cardiometabolic risk factors and alters gut microbiota in metabolic syndrome patients","volume":"106","author":"Guo","year":"2021","journal-title":"J Clin Endocrinol 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