Injections of okadaic acid, but not beta-amyloid peptide, induce Alz-50 immunoreactive dystrophic neurites in the cerebral cortex of sheep

P. T. Nelson; C. B. Saper

doi:10.1016/0304-3940(96)12563-5

Injections of okadaic acid, but not beta-amyloid peptide, induce Alz-50 immunoreactive dystrophic neurites in the cerebral cortex of sheep

P. T. Nelson, C. B. Saper

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

12 Scopus citations

Abstract

In an attempt to produce an animal model of neurofibrillary degeneration of the Alzheimer type, okadaic acid (a phosphatase inhibitor) and beta-amyloid peptide (1-40) were microinjected into the cerebral cortex of six adult sheep. After survivals varying from 1 day to 3 months, the injection sites and adjacent areas were evaluated using light microscopic immunocytochemistry. Near sites of implantation of crystalline okadaic acid, the Alz-50 monoclonal antibody stained twisted, dystrophic neurites. None of the beta-amyloid peptide injections caused neurofibrillary pathology. However, immunohistochemical analysis revealed no detectable beta-amyloid peptide remaining in the neuropil, even at 1 day, indicating rapid clearance of the beta-amyloid peptide. The induction of Alz-50 immunoreactive dystrophic neurites by okadaic acid in sheep represents a novel animal model of Alzheimer's neurofibrillary pathology.

Original language	English
Pages (from-to)	77-80
Number of pages	4
Journal	Neuroscience Letters
Volume	208
Issue number	2
DOIs	https://doi.org/10.1016/0304-3940(96)12563-5
State	Published - Apr 19 1996

Bibliographical note

Funding Information:
We thank Drs. Peter Davies, Dennis Selkoe, and R. Benoit for generously providing antisera for the current experiments; Drs. Alfredo Lorenzo and Bruce Yankner for flAP peptide; and Quan Hue Ha for excellent technical assistance. This work was supported by grants from the Fidelity Foundation and USPHS grant AG 12856.

Funding

We thank Drs. Peter Davies, Dennis Selkoe, and R. Benoit for generously providing antisera for the current experiments; Drs. Alfredo Lorenzo and Bruce Yankner for flAP peptide; and Quan Hue Ha for excellent technical assistance. This work was supported by grants from the Fidelity Foundation and USPHS grant AG 12856.

Funders	Funder number
National Institute on Aging	R01AG012856
National Institute on Aging
Fidelity Foundation
U.S. Public Health Service

Keywords

Alz-50
Alzheimer's disease
Tau
brain
neurofibrillary tangles
okadaic acid
sheep

ASJC Scopus subject areas

General Neuroscience

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10.1016/0304-3940(96)12563-5

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title = "Injections of okadaic acid, but not beta-amyloid peptide, induce Alz-50 immunoreactive dystrophic neurites in the cerebral cortex of sheep",

abstract = "In an attempt to produce an animal model of neurofibrillary degeneration of the Alzheimer type, okadaic acid (a phosphatase inhibitor) and beta-amyloid peptide (1-40) were microinjected into the cerebral cortex of six adult sheep. After survivals varying from 1 day to 3 months, the injection sites and adjacent areas were evaluated using light microscopic immunocytochemistry. Near sites of implantation of crystalline okadaic acid, the Alz-50 monoclonal antibody stained twisted, dystrophic neurites. None of the beta-amyloid peptide injections caused neurofibrillary pathology. However, immunohistochemical analysis revealed no detectable beta-amyloid peptide remaining in the neuropil, even at 1 day, indicating rapid clearance of the beta-amyloid peptide. The induction of Alz-50 immunoreactive dystrophic neurites by okadaic acid in sheep represents a novel animal model of Alzheimer's neurofibrillary pathology.",

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author = "Nelson, {P. T.} and Saper, {C. B.}",

note = "Funding Information: We thank Drs. Peter Davies, Dennis Selkoe, and R. Benoit for generously providing antisera for the current experiments; Drs. Alfredo Lorenzo and Bruce Yankner for flAP peptide; and Quan Hue Ha for excellent technical assistance. This work was supported by grants from the Fidelity Foundation and USPHS grant AG 12856.",

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Y1 - 1996/4/19

N2 - In an attempt to produce an animal model of neurofibrillary degeneration of the Alzheimer type, okadaic acid (a phosphatase inhibitor) and beta-amyloid peptide (1-40) were microinjected into the cerebral cortex of six adult sheep. After survivals varying from 1 day to 3 months, the injection sites and adjacent areas were evaluated using light microscopic immunocytochemistry. Near sites of implantation of crystalline okadaic acid, the Alz-50 monoclonal antibody stained twisted, dystrophic neurites. None of the beta-amyloid peptide injections caused neurofibrillary pathology. However, immunohistochemical analysis revealed no detectable beta-amyloid peptide remaining in the neuropil, even at 1 day, indicating rapid clearance of the beta-amyloid peptide. The induction of Alz-50 immunoreactive dystrophic neurites by okadaic acid in sheep represents a novel animal model of Alzheimer's neurofibrillary pathology.

AB - In an attempt to produce an animal model of neurofibrillary degeneration of the Alzheimer type, okadaic acid (a phosphatase inhibitor) and beta-amyloid peptide (1-40) were microinjected into the cerebral cortex of six adult sheep. After survivals varying from 1 day to 3 months, the injection sites and adjacent areas were evaluated using light microscopic immunocytochemistry. Near sites of implantation of crystalline okadaic acid, the Alz-50 monoclonal antibody stained twisted, dystrophic neurites. None of the beta-amyloid peptide injections caused neurofibrillary pathology. However, immunohistochemical analysis revealed no detectable beta-amyloid peptide remaining in the neuropil, even at 1 day, indicating rapid clearance of the beta-amyloid peptide. The induction of Alz-50 immunoreactive dystrophic neurites by okadaic acid in sheep represents a novel animal model of Alzheimer's neurofibrillary pathology.

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KW - Tau

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KW - neurofibrillary tangles

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Injections of okadaic acid, but not beta-amyloid peptide, induce Alz-50 immunoreactive dystrophic neurites in the cerebral cortex of sheep

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

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