Detection of elevated levels of soluble α-synuclein oligomers in post-mortem brain extracts from patients with dementia with Lewy bodies

Biomedical and Life Sciences

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https://doi.org/10.1093/brain/awn349
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Keywords

Aged, Aged, 80 and over, Alzheimer Disease, Amyloid beta-Peptides, Antibody Specificity, Brain, Enzyme-Linked Immunosorbent Assay, Female, Humans, Lewy Body Disease, Male, Middle Aged, Solubility, alpha-Synuclein, tau Proteins

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Detection of elevated levels of soluble α-synuclein oligomers in post-mortem brain extracts from patients with dementia with Lewy bodies. / Paleologou, Katerina E; Kragh, Christine L; Mann, David M A et al.
In: Brain, Vol. 132, No. 4, 2009, p. 1093-1101.

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Bibtex

@article{7879451238e44176b83b9d780789894e,

title = "Detection of elevated levels of soluble α-synuclein oligomers in post-mortem brain extracts from patients with dementia with Lewy bodies",

abstract = "A number of neurodegenerative diseases including Parkinson's disease, dementia with Lewy bodies (DLB) and multiple system atrophy are characterized by the formation and intraneuronal accumulation of fibrillar aggregates of alpha-synuclein (alpha-syn) protein in affected brain regions. These and other findings suggest that the accumulation of alpha-syn in the brain plays an important role in the pathogenesis of these diseases. However, more recently it has been reported that early amyloid aggregates or 'soluble oligomers' are the pathogenic species that lead to neurodegeneration and neuronal cell death rather than the later 'mature fibrils'. In this study, we investigated the presence of alpha-syn oligomers in brain lysates prepared from frozen post-mortem brains of normal, Alzheimer's disease and DLB patients. The brain extracts were subjected to high speed centrifugation, to remove insoluble alpha-syn aggregates, followed by specific detection of soluble oligomers in the supernatants by employing FILA-1, an antibody that specifically binds to alpha-syn aggregates, but not to alpha-syn monomers, or to tau or beta-amyloid aggregates. Using this novel enzyme-linked immunosorbent assay (ELISA) method to quantify the amounts of alpha-syn oligomers in the brain extracts, our data clearly show an increase in the levels of soluble oligomers of alpha-syn in the DLB brains compared to those with Alzheimer's disease and the controls (P <0.0001). Our findings provide strong evidence to support the contention that elevated soluble oligomers of alpha-syn are involved in the pathogenesis of DLB. Furthermore, these findings establish FILA-1 as a very sensitive tool for the detection of oligomeric forms of alpha-syn in human brain lysates.",

keywords = "Aged, Aged, 80 and over, Alzheimer Disease, Amyloid beta-Peptides, Antibody Specificity, Brain, Enzyme-Linked Immunosorbent Assay, Female, Humans, Lewy Body Disease, Male, Middle Aged, Solubility, alpha-Synuclein, tau Proteins",

author = "Paleologou, {Katerina E} and Kragh, {Christine L} and Mann, {David M A} and Salem, {Sultan A} and Rania Al-Shami and David Allsop and Hassan, {Ahmed H} and Jensen, {Poul H} and El-Agnaf, {Omar M A}",

year = "2009",

doi = "10.1093/brain/awn349",

language = "English",

volume = "132",

pages = "1093--1101",

journal = "Brain",

issn = "1460-2156",

publisher = "Oxford University Press",

number = "4",

}

RIS

TY - JOUR

T1 - Detection of elevated levels of soluble α-synuclein oligomers in post-mortem brain extracts from patients with dementia with Lewy bodies

AU - Paleologou, Katerina E

AU - Kragh, Christine L

AU - Mann, David M A

AU - Salem, Sultan A

AU - Al-Shami, Rania

AU - Allsop, David

AU - Hassan, Ahmed H

AU - Jensen, Poul H

AU - El-Agnaf, Omar M A

PY - 2009

Y1 - 2009

N2 - A number of neurodegenerative diseases including Parkinson's disease, dementia with Lewy bodies (DLB) and multiple system atrophy are characterized by the formation and intraneuronal accumulation of fibrillar aggregates of alpha-synuclein (alpha-syn) protein in affected brain regions. These and other findings suggest that the accumulation of alpha-syn in the brain plays an important role in the pathogenesis of these diseases. However, more recently it has been reported that early amyloid aggregates or 'soluble oligomers' are the pathogenic species that lead to neurodegeneration and neuronal cell death rather than the later 'mature fibrils'. In this study, we investigated the presence of alpha-syn oligomers in brain lysates prepared from frozen post-mortem brains of normal, Alzheimer's disease and DLB patients. The brain extracts were subjected to high speed centrifugation, to remove insoluble alpha-syn aggregates, followed by specific detection of soluble oligomers in the supernatants by employing FILA-1, an antibody that specifically binds to alpha-syn aggregates, but not to alpha-syn monomers, or to tau or beta-amyloid aggregates. Using this novel enzyme-linked immunosorbent assay (ELISA) method to quantify the amounts of alpha-syn oligomers in the brain extracts, our data clearly show an increase in the levels of soluble oligomers of alpha-syn in the DLB brains compared to those with Alzheimer's disease and the controls (P <0.0001). Our findings provide strong evidence to support the contention that elevated soluble oligomers of alpha-syn are involved in the pathogenesis of DLB. Furthermore, these findings establish FILA-1 as a very sensitive tool for the detection of oligomeric forms of alpha-syn in human brain lysates.

AB - A number of neurodegenerative diseases including Parkinson's disease, dementia with Lewy bodies (DLB) and multiple system atrophy are characterized by the formation and intraneuronal accumulation of fibrillar aggregates of alpha-synuclein (alpha-syn) protein in affected brain regions. These and other findings suggest that the accumulation of alpha-syn in the brain plays an important role in the pathogenesis of these diseases. However, more recently it has been reported that early amyloid aggregates or 'soluble oligomers' are the pathogenic species that lead to neurodegeneration and neuronal cell death rather than the later 'mature fibrils'. In this study, we investigated the presence of alpha-syn oligomers in brain lysates prepared from frozen post-mortem brains of normal, Alzheimer's disease and DLB patients. The brain extracts were subjected to high speed centrifugation, to remove insoluble alpha-syn aggregates, followed by specific detection of soluble oligomers in the supernatants by employing FILA-1, an antibody that specifically binds to alpha-syn aggregates, but not to alpha-syn monomers, or to tau or beta-amyloid aggregates. Using this novel enzyme-linked immunosorbent assay (ELISA) method to quantify the amounts of alpha-syn oligomers in the brain extracts, our data clearly show an increase in the levels of soluble oligomers of alpha-syn in the DLB brains compared to those with Alzheimer's disease and the controls (P <0.0001). Our findings provide strong evidence to support the contention that elevated soluble oligomers of alpha-syn are involved in the pathogenesis of DLB. Furthermore, these findings establish FILA-1 as a very sensitive tool for the detection of oligomeric forms of alpha-syn in human brain lysates.

KW - Aged

KW - Aged, 80 and over

KW - Alzheimer Disease

KW - Amyloid beta-Peptides

KW - Antibody Specificity

KW - Brain

KW - Enzyme-Linked Immunosorbent Assay

KW - Female

KW - Humans

KW - Lewy Body Disease

KW - Male

KW - Middle Aged

KW - Solubility

KW - alpha-Synuclein

KW - tau Proteins

UR - http://www.scopus.com/inward/record.url?scp=65249162241&partnerID=8YFLogxK

U2 - 10.1093/brain/awn349

DO - 10.1093/brain/awn349

M3 - Journal article

C2 - 19155272

VL - 132

SP - 1093

EP - 1101

JO - Brain

JF - Brain

SN - 1460-2156

IS - 4

ER -

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