TY - JOUR
T1 - Amyloid-β peptide and oligomers in the brain and cerebrospinal fluid of aged canines
AU - Head, Elizabeth
AU - Pop, Viorela
AU - Sarsoza, Floyd
AU - Kayed, Rakez
AU - Beckett, Tina L.
AU - Studzinski, Christa M.
AU - Tomic, Jennifer L.
AU - Glabe, Charles G.
AU - Murphy, M. Paul
PY - 2010
Y1 - 2010
N2 - The study of Alzheimer's disease (AD) pathogenesis requires the use of animal models that develop some amount of amyloid pathology in the brain. Aged canines (beagles) naturally accumulate human-type amyloid-β peptide (Aβ) and develop parallel declines in cognitive function. However, the type and quantity of biochemically extracted Aβ in brain and cerebrospinal fluid (CSF), its link to aging, and similarity to human aging has not been examined systematically. Thirty beagles, aged 4.5-15.7 years, were studied. Aβ{40} and Aβ{42} were measured in CSF by ELISA, and from SDS and formic acid extracted prefrontal cortex. A sample of the contralateral hemisphere, used to assess immunohistochemical amyloid load, was used for comparison. In the brain, increases in Aβ{42} were detected at a younger age, prior to increases in Aβ{40}, and were correlated with an increased amyloid load. In the CSF, Aβ{42} decreased with age while Aβ{40} levels remained constant. The CSF Aβ{42/40} ratio was also a good predictor of the amount of Aβ in the brain. The amount of soluble oligomers in CSF was inversely related to brain extractable Aβ, whereas oligomers in the brain were correlated with SDS soluble Aβ{42}. These findings indicate that the Aβ in the brain of the aged canine exhibits patterns that mirror Aβ deposited in the human brain. These parallels support the idea that the aged canine is a useful intermediate between transgenic mice and humans for studying the development of amyloid pathology and is a potentially useful model for the refinement of therapeutic interventions.
AB - The study of Alzheimer's disease (AD) pathogenesis requires the use of animal models that develop some amount of amyloid pathology in the brain. Aged canines (beagles) naturally accumulate human-type amyloid-β peptide (Aβ) and develop parallel declines in cognitive function. However, the type and quantity of biochemically extracted Aβ in brain and cerebrospinal fluid (CSF), its link to aging, and similarity to human aging has not been examined systematically. Thirty beagles, aged 4.5-15.7 years, were studied. Aβ{40} and Aβ{42} were measured in CSF by ELISA, and from SDS and formic acid extracted prefrontal cortex. A sample of the contralateral hemisphere, used to assess immunohistochemical amyloid load, was used for comparison. In the brain, increases in Aβ{42} were detected at a younger age, prior to increases in Aβ{40}, and were correlated with an increased amyloid load. In the CSF, Aβ{42} decreased with age while Aβ{40} levels remained constant. The CSF Aβ{42/40} ratio was also a good predictor of the amount of Aβ in the brain. The amount of soluble oligomers in CSF was inversely related to brain extractable Aβ, whereas oligomers in the brain were correlated with SDS soluble Aβ{42}. These findings indicate that the Aβ in the brain of the aged canine exhibits patterns that mirror Aβ deposited in the human brain. These parallels support the idea that the aged canine is a useful intermediate between transgenic mice and humans for studying the development of amyloid pathology and is a potentially useful model for the refinement of therapeutic interventions.
KW - Alzheimer's disease
KW - amyloid-β peptide
KW - amyloid-β protein precursor
KW - beagle
KW - cerebrospinal fluid
KW - dog
KW - oligomer
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U2 - 10.3233/JAD-2010-1397
DO - 10.3233/JAD-2010-1397
M3 - Article
C2 - 20164551
AN - SCOPUS:77954507297
SN - 1387-2877
VL - 20
SP - 637
EP - 646
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
IS - 2
ER -