Cargando…

Lipid Metabolism in Late-Onset Alzheimer’s Disease Differs from Patients Presenting with Other Dementia Phenotypes

Abnormal cerebrospinal fluid (CSF) levels of β-amyloid peptides (Aβ(42)) and Tau and cognitive decline are typical characteristics of Alzheimer’s disease (AD). Since dysregulation in lipid metabolism accompanies abnormal amyloid formation, we quantified glycerophospholipids (GP) and sphingolipids (S...

Descripción completa

Detalles Bibliográficos
Autores principales: Sarrafpour, Syena, Ormseth, Cora, Chiang, Abby, Arakaki, Xianghong, Harrington, Michael, Fonteh, Alfred
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6603882/
https://www.ncbi.nlm.nih.gov/pubmed/31195602
http://dx.doi.org/10.3390/ijerph16111995
_version_ 1783431607662673920
author Sarrafpour, Syena
Ormseth, Cora
Chiang, Abby
Arakaki, Xianghong
Harrington, Michael
Fonteh, Alfred
author_facet Sarrafpour, Syena
Ormseth, Cora
Chiang, Abby
Arakaki, Xianghong
Harrington, Michael
Fonteh, Alfred
author_sort Sarrafpour, Syena
collection PubMed
description Abnormal cerebrospinal fluid (CSF) levels of β-amyloid peptides (Aβ(42)) and Tau and cognitive decline are typical characteristics of Alzheimer’s disease (AD). Since dysregulation in lipid metabolism accompanies abnormal amyloid formation, we quantified glycerophospholipids (GP) and sphingolipids (SP) in CSF fractions from participants with late-onset AD (LOAD, n = 29) or with Other Dementia (OD, n = 10) to determine if alterations in lipid metabolism account for pathological differences. Aβ(42) and total Tau levels were determined using a sandwich ELISA. Liposomal-based fluorescent assays were used to measure phospholipase A(2) (PLA(2)) and acid or neutral sphingomyelinase (aSMase, nSMase) activities. Supernatant fluid (SF) and nanoparticle (NP) lipids were quantified using LC-MS/MS. Although CSF Aβ(42) and Tau levels are similar, phosphatidylserine (PS) in SF and ceramide (CM) levels in NP are significantly higher in OD compared with LOAD. The aSMase but not the nSMase activity is higher in OD. PLA(2) activity in CSF from OD subjects positively correlates with several GP classes in SF and NP fractions but not in LOAD fractions. Our data indicate differences in CSF lipid metabolism between dementia variants. Higher levels of inflammatory and apoptotic lipids may induce faster neuronal death, resulting in the earlier cognitive decline in patients with OD phenotypes.
format Online
Article
Text
id pubmed-6603882
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-66038822019-07-17 Lipid Metabolism in Late-Onset Alzheimer’s Disease Differs from Patients Presenting with Other Dementia Phenotypes Sarrafpour, Syena Ormseth, Cora Chiang, Abby Arakaki, Xianghong Harrington, Michael Fonteh, Alfred Int J Environ Res Public Health Article Abnormal cerebrospinal fluid (CSF) levels of β-amyloid peptides (Aβ(42)) and Tau and cognitive decline are typical characteristics of Alzheimer’s disease (AD). Since dysregulation in lipid metabolism accompanies abnormal amyloid formation, we quantified glycerophospholipids (GP) and sphingolipids (SP) in CSF fractions from participants with late-onset AD (LOAD, n = 29) or with Other Dementia (OD, n = 10) to determine if alterations in lipid metabolism account for pathological differences. Aβ(42) and total Tau levels were determined using a sandwich ELISA. Liposomal-based fluorescent assays were used to measure phospholipase A(2) (PLA(2)) and acid or neutral sphingomyelinase (aSMase, nSMase) activities. Supernatant fluid (SF) and nanoparticle (NP) lipids were quantified using LC-MS/MS. Although CSF Aβ(42) and Tau levels are similar, phosphatidylserine (PS) in SF and ceramide (CM) levels in NP are significantly higher in OD compared with LOAD. The aSMase but not the nSMase activity is higher in OD. PLA(2) activity in CSF from OD subjects positively correlates with several GP classes in SF and NP fractions but not in LOAD fractions. Our data indicate differences in CSF lipid metabolism between dementia variants. Higher levels of inflammatory and apoptotic lipids may induce faster neuronal death, resulting in the earlier cognitive decline in patients with OD phenotypes. MDPI 2019-06-05 2019-06 /pmc/articles/PMC6603882/ /pubmed/31195602 http://dx.doi.org/10.3390/ijerph16111995 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sarrafpour, Syena
Ormseth, Cora
Chiang, Abby
Arakaki, Xianghong
Harrington, Michael
Fonteh, Alfred
Lipid Metabolism in Late-Onset Alzheimer’s Disease Differs from Patients Presenting with Other Dementia Phenotypes
title Lipid Metabolism in Late-Onset Alzheimer’s Disease Differs from Patients Presenting with Other Dementia Phenotypes
title_full Lipid Metabolism in Late-Onset Alzheimer’s Disease Differs from Patients Presenting with Other Dementia Phenotypes
title_fullStr Lipid Metabolism in Late-Onset Alzheimer’s Disease Differs from Patients Presenting with Other Dementia Phenotypes
title_full_unstemmed Lipid Metabolism in Late-Onset Alzheimer’s Disease Differs from Patients Presenting with Other Dementia Phenotypes
title_short Lipid Metabolism in Late-Onset Alzheimer’s Disease Differs from Patients Presenting with Other Dementia Phenotypes
title_sort lipid metabolism in late-onset alzheimer’s disease differs from patients presenting with other dementia phenotypes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6603882/
https://www.ncbi.nlm.nih.gov/pubmed/31195602
http://dx.doi.org/10.3390/ijerph16111995
work_keys_str_mv AT sarrafpoursyena lipidmetabolisminlateonsetalzheimersdiseasediffersfrompatientspresentingwithotherdementiaphenotypes
AT ormsethcora lipidmetabolisminlateonsetalzheimersdiseasediffersfrompatientspresentingwithotherdementiaphenotypes
AT chiangabby lipidmetabolisminlateonsetalzheimersdiseasediffersfrompatientspresentingwithotherdementiaphenotypes
AT arakakixianghong lipidmetabolisminlateonsetalzheimersdiseasediffersfrompatientspresentingwithotherdementiaphenotypes
AT harringtonmichael lipidmetabolisminlateonsetalzheimersdiseasediffersfrompatientspresentingwithotherdementiaphenotypes
AT fontehalfred lipidmetabolisminlateonsetalzheimersdiseasediffersfrompatientspresentingwithotherdementiaphenotypes