Apolipoprotein E isoform-dependent amyloid deposition and neuritic degeneration in a mouse model of Alzheimer's disease

David M. Holtzman; Kelly R. Bales; Tanya Tenkova; Anne M. Fagan; Maia Parsadanian; Leah J. Sartorius; Brian Mackey; John Olney; Daniel McKeel; David Wozniak; Steven M. Paul

doi:10.1073/pnas.050004797

Apolipoprotein E isoform-dependent amyloid deposition and neuritic degeneration in a mouse model of Alzheimer's disease

David M. Holtzman
, Kelly R. Bales
, Tanya Tenkova
, Anne M. Fagan
, Maia Parsadanian
, Leah J. Sartorius
, Brian Mackey
, John Olney
, Daniel McKeel
, David Wozniak
, Steven M. Paul

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

804 Scopus citations

Abstract

Apolipoprotein E (apoE) alleles determine the age-adjusted relative risk (ε4 > ε3) for Alzheimer's disease (AD). ApoE may affect AD pathogenesis by promoting deposition of the amyloid-β (Aβ) peptide and its conversion to a fibrillar form. To determine the effect of apoE on Aβ deposition and AD pathology, we compared APP(V717F) transgenic (TG) mice expressing mouse, human, or no apoE (apoE(-/-)). A severe, plaque-associated neuritic dystrophy developed in APP(V717F) TG mice expressing mouse or human apoE. Though significant levels of Aβ deposition also occurred in APP(V717F) TG, apoE(-/- ) mice, neuritic degeneration was virtually absent. Expression of apoE3 and apoE4 in APP(V717F) TG, apoE(-/-) mice resulted in fibrillar Aβ deposits and neuritic plaques by 15 months of age and substantially (>10-fold) more fibrillar deposits were observed in apoE4-expressing APP(V717F) TG mice. Our data demonstrate a critical and isoform-specific role for apoE in neuritic plaque formation, a pathological hallmark of AD.

Original language	English
Pages (from-to)	2892-2897
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	97
Issue number	6
DOIs	https://doi.org/10.1073/pnas.050004797
State	Published - Mar 14 2000

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10.1073/pnas.050004797

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Holtzman, D. M., Bales, K. R., Tenkova, T., Fagan, A. M., Parsadanian, M., Sartorius, L. J., Mackey, B., Olney, J., McKeel, D., Wozniak, D., & Paul, S. M. (2000). Apolipoprotein E isoform-dependent amyloid deposition and neuritic degeneration in a mouse model of Alzheimer's disease. Proceedings of the National Academy of Sciences of the United States of America, 97(6), 2892-2897. https://doi.org/10.1073/pnas.050004797

@article{c83e9e7e92214ffebbd53b7b2df8f07a,

title = "Apolipoprotein E isoform-dependent amyloid deposition and neuritic degeneration in a mouse model of Alzheimer's disease",

abstract = "Apolipoprotein E (apoE) alleles determine the age-adjusted relative risk (ε4 > ε3) for Alzheimer's disease (AD). ApoE may affect AD pathogenesis by promoting deposition of the amyloid-β (Aβ) peptide and its conversion to a fibrillar form. To determine the effect of apoE on Aβ deposition and AD pathology, we compared APP(V717F) transgenic (TG) mice expressing mouse, human, or no apoE (apoE(-/-)). A severe, plaque-associated neuritic dystrophy developed in APP(V717F) TG mice expressing mouse or human apoE. Though significant levels of Aβ deposition also occurred in APP(V717F) TG, apoE(-/- ) mice, neuritic degeneration was virtually absent. Expression of apoE3 and apoE4 in APP(V717F) TG, apoE(-/-) mice resulted in fibrillar Aβ deposits and neuritic plaques by 15 months of age and substantially (>10-fold) more fibrillar deposits were observed in apoE4-expressing APP(V717F) TG mice. Our data demonstrate a critical and isoform-specific role for apoE in neuritic plaque formation, a pathological hallmark of AD.",

author = "Holtzman, \{David M.\} and Bales, \{Kelly R.\} and Tanya Tenkova and Fagan, \{Anne M.\} and Maia Parsadanian and Sartorius, \{Leah J.\} and Brian Mackey and John Olney and Daniel McKeel and David Wozniak and Paul, \{Steven M.\}",

year = "2000",

month = mar,

day = "14",

doi = "10.1073/pnas.050004797",

language = "English",

volume = "97",

pages = "2892--2897",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

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Holtzman, DM, Bales, KR, Tenkova, T, Fagan, AM, Parsadanian, M, Sartorius, LJ, Mackey, B, Olney, J, McKeel, D, Wozniak, D & Paul, SM 2000, 'Apolipoprotein E isoform-dependent amyloid deposition and neuritic degeneration in a mouse model of Alzheimer's disease', Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 6, pp. 2892-2897. https://doi.org/10.1073/pnas.050004797

Apolipoprotein E isoform-dependent amyloid deposition and neuritic degeneration in a mouse model of Alzheimer's disease. / Holtzman, David M.; Bales, Kelly R.; Tenkova, Tanya et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 97, No. 6, 14.03.2000, p. 2892-2897.

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

TY - JOUR

T1 - Apolipoprotein E isoform-dependent amyloid deposition and neuritic degeneration in a mouse model of Alzheimer's disease

AU - Holtzman, David M.

AU - Bales, Kelly R.

AU - Tenkova, Tanya

AU - Fagan, Anne M.

AU - Parsadanian, Maia

AU - Sartorius, Leah J.

AU - Mackey, Brian

AU - Olney, John

AU - McKeel, Daniel

AU - Wozniak, David

AU - Paul, Steven M.

PY - 2000/3/14

Y1 - 2000/3/14

N2 - Apolipoprotein E (apoE) alleles determine the age-adjusted relative risk (ε4 > ε3) for Alzheimer's disease (AD). ApoE may affect AD pathogenesis by promoting deposition of the amyloid-β (Aβ) peptide and its conversion to a fibrillar form. To determine the effect of apoE on Aβ deposition and AD pathology, we compared APP(V717F) transgenic (TG) mice expressing mouse, human, or no apoE (apoE(-/-)). A severe, plaque-associated neuritic dystrophy developed in APP(V717F) TG mice expressing mouse or human apoE. Though significant levels of Aβ deposition also occurred in APP(V717F) TG, apoE(-/- ) mice, neuritic degeneration was virtually absent. Expression of apoE3 and apoE4 in APP(V717F) TG, apoE(-/-) mice resulted in fibrillar Aβ deposits and neuritic plaques by 15 months of age and substantially (>10-fold) more fibrillar deposits were observed in apoE4-expressing APP(V717F) TG mice. Our data demonstrate a critical and isoform-specific role for apoE in neuritic plaque formation, a pathological hallmark of AD.

AB - Apolipoprotein E (apoE) alleles determine the age-adjusted relative risk (ε4 > ε3) for Alzheimer's disease (AD). ApoE may affect AD pathogenesis by promoting deposition of the amyloid-β (Aβ) peptide and its conversion to a fibrillar form. To determine the effect of apoE on Aβ deposition and AD pathology, we compared APP(V717F) transgenic (TG) mice expressing mouse, human, or no apoE (apoE(-/-)). A severe, plaque-associated neuritic dystrophy developed in APP(V717F) TG mice expressing mouse or human apoE. Though significant levels of Aβ deposition also occurred in APP(V717F) TG, apoE(-/- ) mice, neuritic degeneration was virtually absent. Expression of apoE3 and apoE4 in APP(V717F) TG, apoE(-/-) mice resulted in fibrillar Aβ deposits and neuritic plaques by 15 months of age and substantially (>10-fold) more fibrillar deposits were observed in apoE4-expressing APP(V717F) TG mice. Our data demonstrate a critical and isoform-specific role for apoE in neuritic plaque formation, a pathological hallmark of AD.

UR - https://www.scopus.com/pages/publications/4243215848

U2 - 10.1073/pnas.050004797

DO - 10.1073/pnas.050004797

M3 - Article

C2 - 10694577

AN - SCOPUS:4243215848

SN - 0027-8424

VL - 97

SP - 2892

EP - 2897

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 6

ER -

Apolipoprotein E isoform-dependent amyloid deposition and neuritic degeneration in a mouse model of Alzheimer's disease

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