title: Anomalies occurring in lipid profiles and protein distribution in frontal cortex lipid rafts in dementia with Lewy bodies disclose neurochemical traits partially shared by Alzheimer's and Parkinson's diseases.
abstract: Lipid rafts are highly dynamic membrane microdomains intimately associated with cell signaling. Compelling evidence has demonstrated that alterations in lipid rafts are associated with neurodegenerative diseases such Alzheimer's disease, but at present, whether alterations in lipid raft microdomains occur in other types of dementia such dementia with Lewy bodies (DLB) remains unknown. Our analyses reveal that lipid rafts from DLB exhibit aberrant lipid profiles including low levels of n-3 long-chain polyunsaturated fatty acids (mainly docosahexaenoic acid), plasmalogens and cholesterol, and reduced unsaturation and peroxidability indexes. As a consequence, lipid raft resident proteins holding principal factors of the β-amyloidogenic pathway, including β-amyloid precursor protein, presenilin 1, β-secretase, and PrP, are redistributed between lipid rafts and nonraft domains in DLB frontal cortex. Meta-analysis discloses certain similarities in the altered composition of lipid rafts between DLB and Parkinson's disease which are in line with the spectrum of Lewy body diseases. In addition, redistribution of proteins linked to the β-amyloidogenic pathway in DLB can facilitate generation of β-amyloid, thus providing mechanistic clues to the intriguing convergence of Alzheimer's disease pathology, particularly β-amyloid deposition, in DLB.
authors: Departamento de Fisiología, Universidad de La Laguna, Tenerife, Spain.
authors: Raquel
authors: R
authors: Marin
authors: Departamento de Biología Animal, Universidad de La Laguna, Tenerife, Spain.
authors: Noemí
authors: N
authors: Fabelo
authors: Instituto Español de Oceanografía, Tenerife, Spain.
authors: Virginia
authors: V
authors: Martín
authors: Instituto Neuropatología, Servicio Anatomía Patológica, Hospital Universitario de Bellvitge, Universidad de Barcelona, CIBERNED, Hospitalet de Llobregat, Spain.
authors: Paula
authors: P
authors: Garcia-Esparcia
authors: Instituto Neuropatología, Servicio Anatomía Patológica, Hospital Universitario de Bellvitge, Universidad de Barcelona, CIBERNED, Hospitalet de Llobregat, Spain.
authors: Isidre
authors: I
authors: Ferrer
authors: Departamento de Biología Animal, Universidad de La Laguna, Tenerife, Spain.
authors: David
authors: D
authors: Quinto-Alemany
authors: Departamento de Biología Animal, Universidad de La Laguna, Tenerife, Spain. Electronic address: madiaz@ull.es.
authors: Mario
authors: M
authors: Díaz
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000378:metabolism; D005260:Female; D005625:Frontal Lobe / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D020961:Lewy Body Disease / Q000378:metabolism*; D050356:Lipid Metabolism; D008297:Male; D021962:Membrane Microdomains / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism*; D010955:Plasmalogens / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D009419:Nerve Tissue Proteins; D010955:Plasmalogens; D004281:Docosahexaenoic Acids; D002784:Cholesterol; D053829:Amyloid Precursor Protein Secretases
keywords: Alzheimer's disease; Amyloid precursor protein; Amyloidogenic processing; Cholesterol; Docosahexaenoic acid; Human brain cortex; Lewy body diseases; Lipid rafts; Parkinson's disease; Plasmalogens; β-secretase