{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T06:17:53Z","timestamp":1783491473568,"version":"3.55.0"},"reference-count":119,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"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. Mol. Neurosci."],"abstract":"<jats:p>\n                    Alzheimer\u2019s disease (AD), the most common cause of dementia in older adults, is characterized by progressive cognitive decline, synaptic dysfunction, and neuronal loss. Among the multifactorial mechanisms implicated in AD, reciprocal interactions between brain-derived neurotrophic factor (BDNF) and amyloid-\n                    <jats:italic>\u03b2<\/jats:italic>\n                    (A\n                    <jats:italic>\u03b2<\/jats:italic>\n                    ) have attracted increasing attention as a convergent axis linking amyloid pathology to impaired neurotrophic support. BDNF promotes neuronal resilience, synaptic plasticity, and cognitive function primarily through the activation of its high-affinity receptor, tropomyosin receptor kinase B (TrkB), and downstream signaling pathways, including PI3K-Akt and MAPK\/ERK. Human postmortem and biomarker studies mainly support associations between reduced BDNF signaling, synaptic dysfunction, and AD-related pathology. In contrast, cell-based and animal studies provide mechanistic evidence that BDNF\/TrkB signaling may influence amyloid precursor protein (APP) processing and neuronal resistance to A\n                    <jats:italic>\u03b2<\/jats:italic>\n                    -induced stress. Conversely, mechanistic studies indicate that A\n                    <jats:italic>\u03b2<\/jats:italic>\n                    accumulation can suppress CREB-dependent BDNF expression, disturb BDNF transport, and impair TrkB receptor function. Thus, the BDNF\u2013A\n                    <jats:italic>\u03b2<\/jats:italic>\n                    relationship is better interpreted as a stage- and context-dependent pathogenic coupling rather than a simple causal loop. This review synthesizes evidence from human studies, animal models, and cellular systems to clarify how BDNF\u2013A\n                    <jats:italic>\u03b2<\/jats:italic>\n                    dysregulation contributes to AD progression and to discuss the translational potential of BDNF-oriented interventions.\n                  <\/jats:p>","DOI":"10.3389\/fnmol.2026.1884003","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:52:28Z","timestamp":1783489948000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["BDNF\u2013amyloid-\u03b2 Axis in Alzheimer\u2019s disease: molecular mechanisms and therapeutic perspectives"],"prefix":"10.3389","volume":"19","author":[{"given":"Fangfang","family":"Liu","sequence":"first","affiliation":[{"name":"Clinical Laboratory, Nanping First Hospital Affiliated to Fujian Medical University","place":["Nanping, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanmao","family":"Huang","sequence":"additional","affiliation":[{"name":"Clinical Laboratory, Nanping First Hospital Affiliated to Fujian Medical University","place":["Nanping, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiping","family":"Wang","sequence":"additional","affiliation":[{"name":"Faculty of Basic Medical Sciences, Department of Basic Medicine, Hainan Vocational University of Science and Technology","place":["Haikou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiyan","family":"Liu","sequence":"additional","affiliation":[{"name":"Clinical Laboratory, Nanping First Hospital Affiliated to Fujian Medical University","place":["Nanping, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haolin","family":"Wu","sequence":"additional","affiliation":[{"name":"International Center for Aging and Cancer, Hainan Medical University","place":["Haikou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haofei","family":"Fan","sequence":"additional","affiliation":[{"name":"International Center for Aging and Cancer, Hainan Medical University","place":["Haikou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,8]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.3233\/JAD-190049","article-title":"Dysregulation of BDNF in prefrontal cortex in Alzheimer's disease","volume":"69","author":"Aarons","year":"2019","journal-title":"J. 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