Aβ aggregation profiles and shifts in APP processing favor amyloidogenesis in canines

Viorela Pop; Elizabeth Head; Nicole C. Berchtold; Charles G. Glabe; Christa M. Studzinski; Adam M. Weidner; M. Paul Murphy; Carl W. Cotman

doi:10.1016/j.neurobiolaging.2010.02.008

Aβ aggregation profiles and shifts in APP processing favor amyloidogenesis in canines

Viorela Pop, Elizabeth Head, Nicole C. Berchtold, Charles G. Glabe, Christa M. Studzinski, Adam M. Weidner, M. Paul Murphy, Carl W. Cotman

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

22 Scopus citations

Abstract

The aged canine is a higher animal model that naturally accumulates β-amyloid (Aβ) and shows age-related cognitive decline. However, profiles of Aβ accumulation in different species (40 vs. 42), its assembly states, and Aβ precursor protein (APP) processing as a function of age remain unexplored. In this study, we show that Aβ increases progressively with age as detected in extracellular plaques and biochemically extractable Aβ40 and Aβ42 species. Soluble oligomeric forms of the peptide, with specific increases in an Aβ oligomer migrating at 56 kDa, also increase with age. Changes in APP processing could potentially explain why Aβ accumulates, and we show age-related shifts toward decreased total APP protein and nonamyloidogenic (α-secretase) processing coupled with increased amyloidogenic (β-secretase) cleavage of APP. Importantly, we describe Aβ pathology in the cingulate and temporal cortex and provide a description of oligomeric Aβ across the canine lifespan. Our findings are in line with observations in the human brain, suggesting that canines are a valuable higher animal model for the study of Aβ pathogenesis.

Original language	English
Pages (from-to)	108-120
Number of pages	13
Journal	Neurobiology of Aging
Volume	33
Issue number	1
DOIs	https://doi.org/10.1016/j.neurobiolaging.2010.02.008
State	Published - Jan 2012

Bibliographical note

Funding Information:
The authors thank the following people for technical assistance and advice: Jennifer Thompson for brain oligomer extractions, Anna Pensalfini for dot blots, Paul Adlard and Wayne Poon for the enzyme activity assays, and Xiaohong Wang for BACE1 Western blots. Funding was provided by NIH grants NS058383 and AG005119 (to MPM), AG12694 , AG17066 (to CWC) and AG032550 (to EH).

Keywords

ADAM10
APP
Abeta star 56 kDa
Beta amyloid
C-terminal fragments of APP
Canine
Cingulate
Dog
Insulin degrading enzyme
Neprilysin
Oligomer
Secretase
Temporal

ASJC Scopus subject areas

General Neuroscience
Aging
Clinical Neurology
Developmental Biology
Geriatrics and Gerontology

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10.1016/j.neurobiolaging.2010.02.008

Cite this

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title = "Aβ aggregation profiles and shifts in APP processing favor amyloidogenesis in canines",

abstract = "The aged canine is a higher animal model that naturally accumulates β-amyloid (Aβ) and shows age-related cognitive decline. However, profiles of Aβ accumulation in different species (40 vs. 42), its assembly states, and Aβ precursor protein (APP) processing as a function of age remain unexplored. In this study, we show that Aβ increases progressively with age as detected in extracellular plaques and biochemically extractable Aβ40 and Aβ42 species. Soluble oligomeric forms of the peptide, with specific increases in an Aβ oligomer migrating at 56 kDa, also increase with age. Changes in APP processing could potentially explain why Aβ accumulates, and we show age-related shifts toward decreased total APP protein and nonamyloidogenic (α-secretase) processing coupled with increased amyloidogenic (β-secretase) cleavage of APP. Importantly, we describe Aβ pathology in the cingulate and temporal cortex and provide a description of oligomeric Aβ across the canine lifespan. Our findings are in line with observations in the human brain, suggesting that canines are a valuable higher animal model for the study of Aβ pathogenesis.",

keywords = "ADAM10, APP, Abeta star 56 kDa, Beta amyloid, C-terminal fragments of APP, Canine, Cingulate, Dog, Insulin degrading enzyme, Neprilysin, Oligomer, Secretase, Temporal",

author = "Viorela Pop and Elizabeth Head and Berchtold, {Nicole C.} and Glabe, {Charles G.} and Studzinski, {Christa M.} and Weidner, {Adam M.} and Murphy, {M. Paul} and Cotman, {Carl W.}",

note = "Funding Information: The authors thank the following people for technical assistance and advice: Jennifer Thompson for brain oligomer extractions, Anna Pensalfini for dot blots, Paul Adlard and Wayne Poon for the enzyme activity assays, and Xiaohong Wang for BACE1 Western blots. Funding was provided by NIH grants NS058383 and AG005119 (to MPM), AG12694 , AG17066 (to CWC) and AG032550 (to EH). ",

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AU - Head, Elizabeth

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AU - Weidner, Adam M.

AU - Murphy, M. Paul

AU - Cotman, Carl W.

N1 - Funding Information: The authors thank the following people for technical assistance and advice: Jennifer Thompson for brain oligomer extractions, Anna Pensalfini for dot blots, Paul Adlard and Wayne Poon for the enzyme activity assays, and Xiaohong Wang for BACE1 Western blots. Funding was provided by NIH grants NS058383 and AG005119 (to MPM), AG12694 , AG17066 (to CWC) and AG032550 (to EH).

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Aβ aggregation profiles and shifts in APP processing favor amyloidogenesis in canines

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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