title: Lipoprotein lipase is a novel amyloid beta (Abeta)-binding protein that promotes glycosaminoglycan-dependent cellular uptake of Abeta in astrocytes.
abstract: Lipoprotein lipase (LPL) is a member of a lipase family known to hydrolyze triglyceride molecules in plasma lipoprotein particles. LPL also plays a role in the binding of lipoprotein particles to cell-surface molecules, including sulfated glycosaminoglycans (GAGs). LPL is predominantly expressed in adipose and muscle but is also highly expressed in the brain where its specific roles are unknown. It has been shown that LPL is colocalized with senile plaques in Alzheimer disease (AD) brains, and its mutations are associated with the severity of AD pathophysiological features. In this study, we identified a novel function of LPL; that is, LPL binds to amyloid β protein (Aβ) and promotes cell-surface association and uptake of Aβ in mouse primary astrocytes. The internalized Aβ was degraded within 12 h, mainly in a lysosomal pathway. We also found that sulfated GAGs were involved in the LPL-mediated cellular uptake of Aβ. Apolipoprotein E was dispensable in the LPL-mediated uptake of Aβ. Our findings indicate that LPL is a novel Aβ-binding protein promoting cellular uptake and subsequent degradation of Aβ.
authors.affiliation: Section of Pathophysiology and Neurobiology, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511, Japan.
authors.forename: Kazuchika
authors.initials: K
authors.lastname: Nishitsuji
authors.forename: Takashi
authors.initials: T
authors.lastname: Hosono
authors.forename: Kenji
authors.initials: K
authors.lastname: Uchimura
authors.forename: Makoto
authors.initials: M
authors.lastname: Michikawa
mesh_terms: D000544:Alzheimer Disease / Q000201:enzymology / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D001253:Astrocytes / Q000201:enzymology*; D002417:Cattle; D002478:Cells, Cultured; D006025:Glycosaminoglycans / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism*; D008247:Lysosomes / Q000201:enzymology / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D006025:Glycosaminoglycans; D008071:Lipoprotein Lipase