{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T19:58:46Z","timestamp":1768939126996,"version":"3.49.0"},"reference-count":67,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000},"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. Aging Neurosci."],"abstract":"<jats:p>\n                    Alzheimer\u2019s disease is widely viewed as a disorder of disturbed amyloid-\n                    <jats:italic>\u03b2<\/jats:italic>\n                    (A\u03b2) homeostasis, yet it remains unclear why A\u03b2 shifts from routine turnover to progressive retention and plaque growth in mid-life. This article advances a mechanochemical hypothesis: that age-related reductions in low-intensity mechanical vibrations in the head and neck\u2014arising from everyday self-vocalization (speech, singing, humming) and physiological, non-hypoxic upper-airway motion during stable sleep\u2014contribute to a gradual narrowing of the A\u03b2 clearance bottleneck. Gentle vibrations transmitted through bone and soft tissue could, in principle, enhance interstitial mixing, reduce local supersaturation and nucleation, increase encounter rates at blood\u2013brain barrier and meningeal-lymphatic interfaces, and augment perivascular and glymphatic transport. A sustained decline in this \u201cintrinsic mechanical vibration\u201d (IMV) dose in mid-life might therefore favor A\u03b2 retention without any change in production. We bring together indirect lines of evidence that are compatible with this view, including sleep and glymphatic studies, neuromodulatory stimulation paradigms, music and singing interventions, and hearing-loss epidemiology, and we discuss domains that at first appear inconsistent, such as voice-heavy occupations and obstructive sleep apnea. We then outline a testable cascade that links behavioral and sleep changes in mid-life to reduced mechanical drive and impaired clearance, and we propose concrete experiments spanning human laboratory studies, clinical trials, animal models, and prospective cohorts. Whether ultimately supported or refuted, this IMV\u2013clearance framework highlights mechanical forces as a potentially modifiable dimension of Alzheimer\u2019s disease risk and treatment response, alongside sleep, vascular health, and cognitive engagement.\n                  <\/jats:p>","DOI":"10.3389\/fnagi.2026.1749562","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T06:32:05Z","timestamp":1768890725000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Intrinsic mechanical vibrations as a missing dimension in amyloid-\u03b2 clearance: a mechanochemical hypothesis for Alzheimer\u2019s disease"],"prefix":"10.3389","volume":"18","author":[{"given":"Xiaochen","family":"Lai","sequence":"first","affiliation":[{"name":"School of Future Technology, Nanjing University of Information Science & Technology","place":["Nanjing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,20]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1186\/s12883-022-02902-z","article-title":"Playing a musical instrument and the risk of dementia among older adults: a systematic review and meta-analysis of prospective cohort studies","volume":"22","author":"Arafa","year":"2022","journal-title":"BMC Neurol."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"836748","DOI":"10.1155\/2014\/836748","article-title":"Playing a musical instrument as a protective factor against dementia and cognitive impairment: a population-based twin study","volume":"2014","author":"Balbag","year":"2014","journal-title":"Int. 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