Premium
P4–082: Heparan sulfate proteoglycan accumulation occurs concurrent with beta–amyloid protein plaque deposition in APP transgenic mouse models of Alzheimer's disease
Author(s) -
Cummings Joel A.,
Masliah Eliezer,
Rockenstein Edward,
Snow Alan D.
Publication year - 2006
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2006.05.1820
Subject(s) - perlecan , genetically modified mouse , heparan sulfate , agrin , fibrillogenesis , proteoglycan , transgene , immunostaining , amyloid (mycology) , senile plaques , microbiology and biotechnology , amyloid precursor protein , biology , pathology , alzheimer's disease , glycosaminoglycan , immunohistochemistry , fibril , immunology , medicine , extracellular matrix , biochemistry , receptor , disease , gene , acetylcholine receptor
Our previous studies over the last 15 years have demonstrated the importance of heparan sulfate (HS) proteoglycans (PGs) and heparan sulfate glycosaminoglycans (GAGs) in the pathogenesis of beta-amyloid protein (A ) fibrillogenesis in Alzheimer’s disease (AD). In the present immunohistochemical study, we used different commercially available HSPG and HS GAG antibodies to discern the temporal relationship between initial HSPG and A accumulation in brains of two different APP transgenic mouse models during amyloid plaque development. Comparisons were made in aging transgenic mice expressing 1) human APP-695 cDNA containing the Swedish (K670M/N671L) mutation (i.e. Tg2576), in which initial amyloid plaque development occurs late (at 7-10 months), and 2) human APP-751 cDNA containing the Swedish and London (V717I) mutations, in which initial plaque development occurs earlier (at 3-5 months of age). Animals were sacrificed every 2-4 weeks at increasing ages from 5 months-24 months for the Tg2576 mice, and from 6-12 months for the double mutation transgenic mice. The results demonstrated that in both mouse models initial HSPG accumulation appeared to occur concurrent and co-localized with A amyloid deposition in brain, as assessed by immunostaining with antibodies that recognize HS GAGs (10E4), agrin, perlecan, and syndecan-2. More robust HSPG immunoreactivity in amyloid plaque deposits was quite evident in the double mutation transgenic mice, compared to the single mutation transgenic mice, suggesting that factors that cause HSPG accumulation may be critical to the timing and initial A fibril and amyloid plaque development in AD and related disorders.