Premium
O2‐06‐04: Intraneuronal Aβ accumulation in Alzheimer's disease
Author(s) -
Poduslo Joseph F.,
Gilles Emily J.,
Ramakrishnan Muthu,
Wengenack Thomas M.,
Curran Geoffry L.,
Kandimalla Karunya K.
Publication year - 2009
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.2009.05.364
Subject(s) - chemistry , fibril , neurodegeneration , endosome , extracellular , thioflavin , biophysics , microbiology and biotechnology , amyloid (mycology) , histidine , biochemistry , amyloid precursor protein , intracellular , alzheimer's disease , biology , medicine , enzyme , disease , inorganic chemistry
species around 56kD; dimer/trimer bands are strong in 2-3 cases. The cterminal antibody CT20 detects a c-terminal fragment at w17kD in AD cases. P-tau aggregates and fragments are detected in the same samples with a series of tau antibodies. Conclusions: These results indicate that multiple APP processing pathways are active in AD synapses and multiple oligomeric assemblies, particularly a 56kD assembly, may contribute to synaptic dysfunction. depolarization with KCl, picrotoxin or by treatment with glycine. Ab, APP and APP C-terminal fragments are assayed by Western blot, ELISA or immunofluorescence. APP trafficking is assayed in primary neurons by live cell imaging using an APP-YFP construct. Results: Synaptic activation resulted in a marked decrease in steady state levels of intraneuronal Ab in treated compared to untreated Tg2576 neurons. In particular, the synaptic activation-induced reduction of intraneuronal Ab42 correlated with recovery of synaptic PSD-95. Live cell imaging revealed a change in transport of YFP-APP in neurons with synaptic activity. Conclusions: Our data show that synaptic activity modulates APP trafficking and reduces the intraneuronal pool of Ab, which may protect against the pathogenesis of AD.