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Low levels of laser light can disassemble A\u03b2. In this study, we investigated the mechanisms that A\u03b2\u2010blocked extracellular space (ECS) induces memory disorders in APP\/PS1 transgenic mice and addressed whether red light (RL) at 630\u2009nm rescues cognitive decline by reducing A\u03b2\u2010disturbed flow of interstitial fluid (ISF).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We compared the heating effects on the brains of rats illuminated with laser light at 630, 680, and 810\u2009nm for 40\u2009minutes, respectively. Then, a light\u2010emitting diode with red light at 630\u2009nm (LED\u2010RL) was selected to illuminate AD mice. The changes in the structure of ECS in the cortex were examined by fluorescent double labeling. The volumes of ECS and flow speed of ISF were quantified by magnetic resonance imaging. Spatial memory behaviors in mice were evaluated by the Morris water maze. Then, the brains were sampled for biochemical analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      RL at 630\u2009nm had the least heating effects than other wavelengths associated with ~49% penetration ratio into the brains. For the molecular mechanisms, A\u03b2 could induce formaldehyde (FA) accumulation by inactivating FA dehydrogenase. Unexpectedly, in turn, FA accelerated A\u03b2 deposition in the ECS. However, LED\u2010RL treatment not only directly destroyed A\u03b2 assembly\n                      <jats:italic>in\u2009vitro<\/jats:italic>\n                      and\n                      <jats:italic>in\u2009vivo<\/jats:italic>\n                      but also activated FA dehydrogenase to degrade FA and attenuated FA\u2010facilitated A\u03b2 aggregation. Subsequently, LED\u2010RL markedly smashed A\u03b2 deposition in the ECS, recovered the flow of ISF, and rescued cognitive functions in AD mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>A\u03b2\u2010obstructed ISF flow is the direct reason for the failure of the developed medicine delivery from superficial into the deep brain in the treatment of AD. The phototherapy of LED\u2010RL improves memory by reducing A\u03b2\u2010blocked ECS and suggests that it is a promising noninvasive approach to treat AD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1016\/j.trci.2019.09.007","type":"journal-article","created":{"date-parts":[[2019,11,3]],"date-time":"2019-11-03T10:53:06Z","timestamp":1572778386000},"page":"671-684","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":71,"title":["New insight into Alzheimer's disease: Light reverses A\u03b2\u2010obstructed interstitial fluid flow and ameliorates memory decline in APP\/PS1 mice"],"prefix":"10.1002","volume":"5","author":[{"given":"Xiangpei","family":"Yue","sequence":"first","affiliation":[{"name":"Laboratory of Alzheimer's Optoelectric Therapy, Alzheimer's Disease Center Beijing Institute for Brain Disorders, Capital Medical University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufei","family":"Mei","sequence":"additional","affiliation":[{"name":"Laboratory of Alzheimer's Optoelectric Therapy, Alzheimer's Disease Center Beijing Institute for Brain Disorders, Capital Medical University Beijing China"},{"name":"School of Basic Medical Sciences, Zhejiang University Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Townsend Family Laboratories The University of British Columbia Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Tong","sequence":"additional","affiliation":[{"name":"School of Engineering, Mechanical Engineering with Renewable Energy. 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