title: Lipoprotein lipase (LPL) is associated with neurite pathology and its levels are markedly reduced in the dentate gyrus of Alzheimer's disease brains.
abstract: Lipoprotein lipase (LPL) is involved in regulation of fatty acid metabolism, and facilitates cellular uptake of lipoproteins, lipids and lipid-soluble vitamins. We evaluated LPL distribution in healthy and Alzheimer's disease (AD) brain tissue and its relative levels in cerebrospinal fluid. LPL immunostaining is widely present in different neuronal subgroups, microglia, astrocytes and oligodendroglia throughout cerebrum, cerebellum and spinal cord. LPL immunoreactivity is also present in leptomeninges, small blood vessels, choroid plexus and ependymal cells, Schwann cells associated with cranial nerves, and in anterior and posterior pituitary. In vitro studies have shown presence of secreted LPL in conditioned media of human cortical neuronal cell line (HCN2) and neuroblastoma cells (SK-N-SH), but not in media of cultured primary human astrocytes. LPL was present in cytoplasmic and nuclear fractions of neuronal cells and astrocytes in vitro. LPL immunoreactivity strongly associates with AD-related pathology, staining diffuse plaques, dystrophic and swollen neurites, possible Hirano bodies and activated glial cells. We observed no staining associated with neurofibrillary tangles or granulovacuolar degeneration. Granule cells of the dentate gyrus and the associated synaptic network showed significantly reduced staining in AD compared to control tissue. LPL was also reduced in AD CSF samples relative to those in controls.
authors.affiliation: Northwest Lipid Metabolism and Diabetes Research Laboratories, Department of Medicine, School of Medicine, University of Washington, Seattle, WA (HG, WD, SMM, JJA, SV).
authors.forename: Huilin
authors.initials: H
authors.lastname: Gong
authors.forename: Weijiang
authors.initials: W
authors.lastname: Dong
authors.forename: Steven W
authors.initials: SW
authors.lastname: Rostad
authors.forename: Santica M
authors.initials: SM
authors.lastname: Marcovina
authors.forename: John J
authors.initials: JJ
authors.lastname: Albers
authors.forename: John D
authors.initials: JD
authors.lastname: Brunzell
authors.forename: Simona
authors.initials: S
authors.lastname: Vuletic
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology* / Q000473:pathology; D018891:Dentate Gyrus / Q000201:enzymology* / Q000473:pathology; D005260:Female; D006801:Humans; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016501:Neurites / Q000201:enzymology* / Q000473:pathology*
chemical_list: D008071:Lipoprotein Lipase
keywords: Alzheimer’s disease; cerebrospinal fluid; glia; human brain; lipoprotein lipase; neurons