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

详细信息    查看全文

• 作者：Raquel Marin^a ; Noemí ; Fabelo^b ; Virginia Martí ; n^c ; Paula Garcia-Esparcia^d ; Isidre Ferrer^d ; David Quinto-Alemany^b ; Mario Dí ; az^b ; ^{madiaz@ull.es}
• 关键词：Lipid rafts ; Docosahexaenoic acid ; Cholesterol ; Plasmalogens ; β-secretase ; Amyloid precursor protein ; Amyloidogenic processing ; Human brain cortex ; Lewy body diseases ; Alzheimer's disease ; Parkinson's disease
• 刊名：Neurobiology of Aging
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：49
• 期：Complete
• 页码：52-59
• 全文大小：1163 K
• 卷排序：49

文摘

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.