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In vivo labelling of hippocampal β‐amyloid in triple‐transgenic mice with a fluorescent acetylcholinesterase inhibitor released from nanoparticles
Author(s) -
Härtig Wolfgang,
Kacza Johannes,
Paulke BerndReiner,
Grosche Jens,
Bauer Ute,
Hoffmann Anke,
Elsinghorst Paul W.,
Gütschow Michael
Publication year - 2010
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2009.07038.x
Subject(s) - in vivo , senile plaques , acetylcholinesterase , chemistry , genetically modified mouse , amyloid precursor protein , basal forebrain , hippocampal formation , cholinergic , amyloid (mycology) , amyloid beta , microbiology and biotechnology , pathology , pharmacology , alzheimer's disease , transgene , biochemistry , biology , neuroscience , medicine , enzyme , inorganic chemistry , disease , gene , peptide
The drastic loss of cholinergic projection neurons in the basal forebrain is a hallmark of Alzheimer’s disease (AD), and drugs most frequently applied for the treatment of dementia include inhibitors of the acetylcholine‐degrading enzyme acetylcholinesterase (AChE). This protein is known to act as a ligand of β‐amyloid (Aβ) in senile plaques, a further neuropathological sign of AD. Recently, we have shown that the fluorescent, heterodimeric AChE inhibitor PE154 allows for the histochemical staining of cortical Aβ plaques in triple‐transgenic (TTG) mice with age‐dependent β‐amyloidosis and tau hyperphosphorylation, an established animal model for aspects of AD. In the present study, we have primarily demonstrated the targeting of Aβ‐immunopositive plaques with PE154 in vivo for 4 h up to 1 week after injection into the hippocampi of 13–20‐month‐old TTG mice. Numerous plaques, double‐stained for PE154 and Aβ‐immunoreactivity, were revealed by confocal laser‐scanning microscopy. Additionally, PE154 targeted hippocampal Aβ deposits in aged TTG mice after injection of carboxylated polyglycidylmethacrylate nanoparticles delivering the fluorescent marker in vivo . Furthermore, biodegradable core‐shell polystyrene/polybutylcyanoacrylate nanoparticles were found to be suitable, alternative vehicles for PE154 as a useful in vivo label of Aβ. Moreover, we were able to demonstrate that PE154 targeted Aβ, but neither phospho‐tau nor reactive astrocytes surrounding the plaques. In conclusion, nanoparticles appear as versatile carriers of AChE inhibitors and other promising drugs for the treatment of AD.