title: The impact of cholesterol, DHA, and sphingolipids on Alzheimer's disease.
abstract: Alzheimer's disease (AD) is a devastating neurodegenerative disorder currently affecting over 35 million people worldwide. Pathological hallmarks of AD are massive amyloidosis, extracellular senile plaques, and intracellular neurofibrillary tangles accompanied by an excessive loss of synapses. Major constituents of senile plaques are 40-42 amino acid long peptides termed β -amyloid (A β ). A β is produced by sequential proteolytic processing of the amyloid precursor protein (APP). APP processing and A β production have been one of the central scopes in AD research in the past. In the last years, lipids and lipid-related issues are more frequently discussed to contribute to the AD pathogenesis. This review summarizes lipid alterations found in AD postmortem brains, AD transgenic mouse models, and the current understanding of how lipids influence the molecular mechanisms leading to AD and A β generation, focusing especially on cholesterol, docosahexaenoic acid (DHA), and sphingolipids/glycosphingolipids.
authors.affiliation: Experimental Neurology, Saarland University, Kirrberger Street 1, 66421 Homburgr, Saar, Germany ; Neurodegeneration and Neurobiology, Saarland University, Kirrberger Street 1, 66421 Homburg, Germany ; Deutsches Institut für DemenzPrävention (DIDP), Saarland University, Kirrberger Street 1, 66421 Homburgr, Saar, Germany.
authors.forename: Marcus O W
authors.initials: MO
authors.lastname: Grimm
authors.affiliation: Experimental Neurology, Saarland University, Kirrberger Street 1, 66421 Homburgr, Saar, Germany.
authors.forename: Valerie C
authors.initials: VC
authors.lastname: Zimmer
authors.affiliation: Experimental Neurology, Saarland University, Kirrberger Street 1, 66421 Homburgr, Saar, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Lehmann
authors.affiliation: Experimental Neurology, Saarland University, Kirrberger Street 1, 66421 Homburgr, Saar, Germany.
authors.forename: Heike S
authors.initials: HS
authors.lastname: Grimm
authors.affiliation: Experimental Neurology, Saarland University, Kirrberger Street 1, 66421 Homburgr, Saar, Germany ; Neurodegeneration and Neurobiology, Saarland University, Kirrberger Street 1, 66421 Homburg, Germany ; Deutsches Institut für DemenzPrävention (DIDP), Saarland University, Kirrberger Street 1, 66421 Homburgr, Saar, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Hartmann
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000686:Amyloidosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics*; D051379:Mice; D013569:Synapses / Q000378:metabolism / Q000473:pathology
chemical_list: C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor