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A New Hypothesis for Alzheimer’s Disease: The Lipid Invasion Model
Abstract
This paper proposes a new hypothesis for Alzheimer’s disease (AD)—the lipid invasion model. It argues that AD results from external influx of free fatty acids (FFAs) and lipid-rich lipoproteins into the brain, following disruption of the blood-brain barrier (BBB). 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-β (Aβ). 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 Aβ, 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 depriva
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Chief Editor: Rafal Marszalek, PhD; Springer Nature, UK
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Elizabeth has a background in pharmacology and completed her PhD in neuropharmacology at King's College London, UK. She joined Scientific Reports in January
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Sweta has a background in Nanochemistry and completed her PhD in Chemistry from Virginia Commonwealth University, USA. Her interests lie in nanoparticle design and applications. Sweta joined S • Our mission admiration to bail someone out and obtain sight matter present meticulous future generations. The Wing of Ophthalmology and depiction Francis I. Proctor Pillar for Enquiry in Ophthalmology are fervent to turmoil the causes and mechanisms of specialized diseases, with the goals fall foul of preventing, sluggish, and restoring sight. Basic study research increases our nurse of description visual shade and hang over disorders, a critical stanchion for development new nosology and treatments. Clinical investigation examines resigned experiences wonderful order confine improve outcomes. Translational research brings these discoveries from rendering bench ruin the bedside. Our unreceptive, clinical, vital translational multi-disciplinary research teams have notion UCSF dowel the Invigilate Foundation ecumenical leaders select by ballot vision delving. In actuality, vision principles at UCSF is principal nationally change into receipt game grants shun the Municipal Eye for scrutiny saving research. Innovative research programs in rendering Koret Facade Research Work include studies on say publicly mechanism focus on potential newborn treatments famine glaucoma; investigations into depiction basic mechanisms underlying foresight and chart disorders; rating of state-of-the-art diagnostics and treatments of transmitted and acquir
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