Different β-amyloid oligomer assemblies in Alzheimer brains correlate with age of disease onset and impaired cholinergic activity

Fuxiang Bao; Linn Wicklund; Pascale N. Lacor; William L. Klein; Agneta Nordberg; Amelia Marutle

doi:10.1016/j.neurobiolaging.2011.05.003

Different β-amyloid oligomer assemblies in Alzheimer brains correlate with age of disease onset and impaired cholinergic activity

Fuxiang Bao, Linn Wicklund, Pascale N. Lacor, William L. Klein, Agneta Nordberg^*, Amelia Marutle

^*Corresponding author for this work

Neurobiology

Research output: Contribution to journal › Article › peer-review

91 Scopus citations

Abstract

In this study, we examined the relationship between various β-amyloid (Aβ) oligomer assemblies in autopsy brain with the levels of fibrillar Aβ and cholinergic synaptic function. Brain tissues obtained from the frontal cortex of 14 Alzheimer's disease (AD) patients grouped into early-onset AD (EOAD) and late-onset AD (LOAD) and 12 age-matched control subjects were used to extract and quantify Aβ oligomers in soluble (TBS), detergent soluble (TBST), and insoluble (GuHCl) fractions. The predominant oligomeric Aβ assemblies detected were dodecamers, decamers, and pentamers, and different patterns of expression were observed between EOAD and LOAD patients. There was no association between any of the detected Aβ oligomer assemblies and fibrillar Aβ levels measured by N-methyl[³H] 2-(40-methylaminophenyl)-6-hydroxy-benzothiazole ([³H]PIB) binding. Levels of pentamers in the soluble fraction significantly correlated with a reduction in choline acetyltransferase activity in AD patients. The number of nicotinic acetylcholine receptors negatively correlated with the total amount of Aβ oligomers in the insoluble fraction in EOAD patients, and with decamers in the soluble fraction in LOAD patients. These novel findings suggest that distinct Aβ oligomers induce impairment of cholinergic neurotransmission in AD pathogenesis.

Original language	English (US)
Pages (from-to)	825.e1-825.e13
Journal	Neurobiology of Aging
Volume	33
Issue number	4
DOIs	https://doi.org/10.1016/j.neurobiolaging.2011.05.003
State	Published - Apr 2012

Funding

This work was supported by the Swedish Research Council (project 05871), The Karolinska Institutet Strategic Neuroscience Program, a grant from Stockholm County Council-Karolinska Institute (ALF grants), Swedish Brain Foundation , Swedish Brain Power , Magnus Bergvalls Foundation , Karolinska Institutet Foundations , the Foundation for Old Servants (Gamla Tjänarinnor), Gun and Bertil Stohnes Foundation , The Dementia Association (Demensfonden) , Alzheimer Foundation in Sweden , The Lars Hierta Memorial Foundation , Olle Engkvist Byggmästare Foundation , Loo and Hans Osterman Foundation , Sigurd and Elsa Goljes Memorial Foundation , and Karolinska Institutet research program agreement with Johnson and Johnson .

Keywords

APPswe mutation
Age
Alzheimer's disease
Autopsy brain
Choline acetyltransferase activity
Early-onset Alzheimer's disease
Fibrillar β-amyloid
Late-onset Alzheimer's disease
Nicotinic acetylcholine receptors
β-amyloid oligomers

ASJC Scopus subject areas

Clinical Neurology
Geriatrics and Gerontology
Aging
General Neuroscience
Developmental Biology

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10.1016/j.neurobiolaging.2011.05.003

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title = "Different β-amyloid oligomer assemblies in Alzheimer brains correlate with age of disease onset and impaired cholinergic activity",

abstract = "In this study, we examined the relationship between various β-amyloid (Aβ) oligomer assemblies in autopsy brain with the levels of fibrillar Aβ and cholinergic synaptic function. Brain tissues obtained from the frontal cortex of 14 Alzheimer's disease (AD) patients grouped into early-onset AD (EOAD) and late-onset AD (LOAD) and 12 age-matched control subjects were used to extract and quantify Aβ oligomers in soluble (TBS), detergent soluble (TBST), and insoluble (GuHCl) fractions. The predominant oligomeric Aβ assemblies detected were dodecamers, decamers, and pentamers, and different patterns of expression were observed between EOAD and LOAD patients. There was no association between any of the detected Aβ oligomer assemblies and fibrillar Aβ levels measured by N-methyl[3H] 2-(40-methylaminophenyl)-6-hydroxy-benzothiazole ([3H]PIB) binding. Levels of pentamers in the soluble fraction significantly correlated with a reduction in choline acetyltransferase activity in AD patients. The number of nicotinic acetylcholine receptors negatively correlated with the total amount of Aβ oligomers in the insoluble fraction in EOAD patients, and with decamers in the soluble fraction in LOAD patients. These novel findings suggest that distinct Aβ oligomers induce impairment of cholinergic neurotransmission in AD pathogenesis.",

keywords = "APPswe mutation, Age, Alzheimer's disease, Autopsy brain, Choline acetyltransferase activity, Early-onset Alzheimer's disease, Fibrillar β-amyloid, Late-onset Alzheimer's disease, Nicotinic acetylcholine receptors, β-amyloid oligomers",

author = "Fuxiang Bao and Linn Wicklund and Lacor, {Pascale N.} and Klein, {William L.} and Agneta Nordberg and Amelia Marutle",

note = "Funding Information: This work was supported by the Swedish Research Council (project 05871), The Karolinska Institutet Strategic Neuroscience Program, a grant from Stockholm County Council-Karolinska Institute (ALF grants), Swedish Brain Foundation , Swedish Brain Power , Magnus Bergvalls Foundation , Karolinska Institutet Foundations , the Foundation for Old Servants (Gamla Tj{\"a}narinnor), Gun and Bertil Stohnes Foundation , The Dementia Association (Demensfonden) , Alzheimer Foundation in Sweden , The Lars Hierta Memorial Foundation , Olle Engkvist Byggm{\"a}stare Foundation , Loo and Hans Osterman Foundation , Sigurd and Elsa Goljes Memorial Foundation , and Karolinska Institutet research program agreement with Johnson and Johnson . ",

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doi = "10.1016/j.neurobiolaging.2011.05.003",

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AU - Wicklund, Linn

AU - Lacor, Pascale N.

AU - Klein, William L.

AU - Nordberg, Agneta

AU - Marutle, Amelia

N1 - Funding Information: This work was supported by the Swedish Research Council (project 05871), The Karolinska Institutet Strategic Neuroscience Program, a grant from Stockholm County Council-Karolinska Institute (ALF grants), Swedish Brain Foundation , Swedish Brain Power , Magnus Bergvalls Foundation , Karolinska Institutet Foundations , the Foundation for Old Servants (Gamla Tjänarinnor), Gun and Bertil Stohnes Foundation , The Dementia Association (Demensfonden) , Alzheimer Foundation in Sweden , The Lars Hierta Memorial Foundation , Olle Engkvist Byggmästare Foundation , Loo and Hans Osterman Foundation , Sigurd and Elsa Goljes Memorial Foundation , and Karolinska Institutet research program agreement with Johnson and Johnson .

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N2 - In this study, we examined the relationship between various β-amyloid (Aβ) oligomer assemblies in autopsy brain with the levels of fibrillar Aβ and cholinergic synaptic function. Brain tissues obtained from the frontal cortex of 14 Alzheimer's disease (AD) patients grouped into early-onset AD (EOAD) and late-onset AD (LOAD) and 12 age-matched control subjects were used to extract and quantify Aβ oligomers in soluble (TBS), detergent soluble (TBST), and insoluble (GuHCl) fractions. The predominant oligomeric Aβ assemblies detected were dodecamers, decamers, and pentamers, and different patterns of expression were observed between EOAD and LOAD patients. There was no association between any of the detected Aβ oligomer assemblies and fibrillar Aβ levels measured by N-methyl[3H] 2-(40-methylaminophenyl)-6-hydroxy-benzothiazole ([3H]PIB) binding. Levels of pentamers in the soluble fraction significantly correlated with a reduction in choline acetyltransferase activity in AD patients. The number of nicotinic acetylcholine receptors negatively correlated with the total amount of Aβ oligomers in the insoluble fraction in EOAD patients, and with decamers in the soluble fraction in LOAD patients. These novel findings suggest that distinct Aβ oligomers induce impairment of cholinergic neurotransmission in AD pathogenesis.

AB - In this study, we examined the relationship between various β-amyloid (Aβ) oligomer assemblies in autopsy brain with the levels of fibrillar Aβ and cholinergic synaptic function. Brain tissues obtained from the frontal cortex of 14 Alzheimer's disease (AD) patients grouped into early-onset AD (EOAD) and late-onset AD (LOAD) and 12 age-matched control subjects were used to extract and quantify Aβ oligomers in soluble (TBS), detergent soluble (TBST), and insoluble (GuHCl) fractions. The predominant oligomeric Aβ assemblies detected were dodecamers, decamers, and pentamers, and different patterns of expression were observed between EOAD and LOAD patients. There was no association between any of the detected Aβ oligomer assemblies and fibrillar Aβ levels measured by N-methyl[3H] 2-(40-methylaminophenyl)-6-hydroxy-benzothiazole ([3H]PIB) binding. Levels of pentamers in the soluble fraction significantly correlated with a reduction in choline acetyltransferase activity in AD patients. The number of nicotinic acetylcholine receptors negatively correlated with the total amount of Aβ oligomers in the insoluble fraction in EOAD patients, and with decamers in the soluble fraction in LOAD patients. These novel findings suggest that distinct Aβ oligomers induce impairment of cholinergic neurotransmission in AD pathogenesis.

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KW - Age

KW - Alzheimer's disease

KW - Autopsy brain

KW - Choline acetyltransferase activity

KW - Early-onset Alzheimer's disease

KW - Fibrillar β-amyloid

KW - Late-onset Alzheimer's disease

KW - Nicotinic acetylcholine receptors

KW - β-amyloid oligomers

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DO - 10.1016/j.neurobiolaging.2011.05.003

M3 - Article

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AN - SCOPUS:84856971964

SN - 0197-4580

VL - 33

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JO - Neurobiology of Aging

JF - Neurobiology of Aging

IS - 4

ER -

Different β-amyloid oligomer assemblies in Alzheimer brains correlate with age of disease onset and impaired cholinergic activity

Abstract

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Keywords

ASJC Scopus subject areas

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