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Genetic and pharmacological evidence of intraneuronal Aβ accumulation in APP transgenic mice
Author(s) -
Philipson Ola,
Lannfelt Lars,
Nilsson Lars N.G.
Publication year - 2009
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2009.08.009
Subject(s) - transgene , genetically modified mouse , microbiology and biotechnology , biology , chemistry , neuroscience , genetics , gene
Intraneuronal punctate immunostaining in Alzheimer's disease brain and amyloid‐β precursor protein (APP) transgenic mice has been suggested to represent Aβ, but this is somewhat controversial. Here we show that both biochemical Aβ levels and intraneuronal immunostaining are reduced in APP transgenic mice when γ‐secretase is inhibited. Moreover, BACE‐1 deficient APP transgenic mice show neither Aβ production nor intraneuronal immunostaining. Our findings suggest that the punctate immunostaining with APP antibodies is due to Aβ that has accumulated inside neurons. Similar type of intraneuronal Aβ accumulation, which precedes senile plaque formation, may link Aβ to tauopathy and neurodegeneration in Alzheimer's disease pathogenesis.