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The lipid invasion model explains how the influx of albumin-bound FFAs via a disrupted BBB induces bioenergetic changes and oxidative stress, stimulates microglia-driven neuroinflammation, and causes anterograde amnesia. It also explains how the influx of external lipoproteins, which are much larger and more lipid-rich, especially more cholesterol-rich, than those normally present in the brain, causes endosomal-lysosomal abnormalities and overproduction of the peptide amyloid-\u03b2 (A\u03b2). This leads to the formation of amyloid plaques and neurofibrillary tangles, the most well-known hallmarks of AD. The lipid invasion model argues that a key role of the BBB is protecting the brain from external lipid access. It shows how the BBB can be damaged by excess A\u03b2, as well as by most other known risk factors for AD, including aging, apolipoprotein E4 ( APOE4), and lifestyle factors such as hypertension, smoking, obesity, diabetes, chronic sleep deprivation, stress, and head injury. The lipid invasion model gives a new rationale for what we already know about AD, explaining its many associated risk factors and neuropathologies, including some that are less well-accounted for in other explanations of AD. It offers new insights and suggests new ways to prevent, detect, and treat this destructive disease and potentially other neurodegenerative diseases.<\/jats:p>","DOI":"10.3233\/adr-210299","type":"journal-article","created":{"date-parts":[[2022,3,15]],"date-time":"2022-03-15T12:02:46Z","timestamp":1647345766000},"page":"129-161","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":49,"title":["A New Hypothesis for Alzheimer\u2019s Disease: The Lipid Invasion Model"],"prefix":"10.1177","volume":"6","author":[{"given":"Jonathan D\u2019Arcy","family":"Rudge","sequence":"first","affiliation":[{"name":"School of Biological Sciences, University of Reading, Reading, Berkshire, United 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