TY - JOUR
T1 - Amyloid phenotype characterization of transgenic mice overexpressing both mutant amyloid precursor protein and mutant presenilin 1 transgenes
AU - McGowan, E.
AU - Sanders, S.
AU - Iwatsubo, T.
AU - Takeuchi, A.
AU - Saido, T.
AU - Zehr, C.
AU - Yu, X.
AU - Uljon, S.
AU - Wang, R.
AU - Mann, D.
AU - Dickson, D.
AU - Duff, K.
N1 - Funding Information:
The authors are grateful to Dr C. Cuello, McGill University, Canada, for the gift of the Aβ1-12 antibody and to Dr. Karen Hsiao, University of Minnesota, for the gift of the Tg2576 line. This work was supported by an Alzheimer’s Association/The Stasia Borsuk Memorial Fund grant (RG1-96-070) to R.W. and an NIH program grant (AG-146133) to K.D.
PY - 1999/8
Y1 - 1999/8
N2 - Doubly transgenic mice (PSAPP) overexpressing mutant APP and PS1 transgenes were examined using antibodies to Aβ subtypes and glial fibrillary acidic protein (GFAP). Visible Aβ deposition began primarily in the cingulate cortex of PSAPP mice at approximately 10 weeks of age. By 6 months, the mice had extensive amyloid deposition throughout the hippocampus and cortex as well as other regions of the brain. Highly congophilic deposits consisting of N-terminal normal and modified forms of Aβ were identified, reminiscent of those found in human AD brain. Both immunohistochemistry and mass spectrometry showed that Aβ42 forms were underrepresented relative to Aβ40, and Aβ43 was undetectable. Deposits were associated with prominent gliosis which increased with age, but in 14-month-old PSAPP mice, GFAP immunoreactivity in the vicinity of amyloid deposits was substantially reduced compared to APP littermates. These mice have considerable utility in the study of the amyloid phenotype of AD.
AB - Doubly transgenic mice (PSAPP) overexpressing mutant APP and PS1 transgenes were examined using antibodies to Aβ subtypes and glial fibrillary acidic protein (GFAP). Visible Aβ deposition began primarily in the cingulate cortex of PSAPP mice at approximately 10 weeks of age. By 6 months, the mice had extensive amyloid deposition throughout the hippocampus and cortex as well as other regions of the brain. Highly congophilic deposits consisting of N-terminal normal and modified forms of Aβ were identified, reminiscent of those found in human AD brain. Both immunohistochemistry and mass spectrometry showed that Aβ42 forms were underrepresented relative to Aβ40, and Aβ43 was undetectable. Deposits were associated with prominent gliosis which increased with age, but in 14-month-old PSAPP mice, GFAP immunoreactivity in the vicinity of amyloid deposits was substantially reduced compared to APP littermates. These mice have considerable utility in the study of the amyloid phenotype of AD.
UR - http://www.scopus.com/inward/record.url?scp=0032886415&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032886415&partnerID=8YFLogxK
U2 - 10.1006/nbdi.1999.0243
DO - 10.1006/nbdi.1999.0243
M3 - Article
C2 - 10448051
AN - SCOPUS:0032886415
SN - 0969-9961
VL - 6
SP - 231
EP - 244
JO - Neurobiology of Disease
JF - Neurobiology of Disease
IS - 4
ER -