Abstract：
:Alzheimer's disease is characterized by the deposition of senile plaques and progressive dementia. The molecular mechanisms that couple plaque deposition to neural system failure, however, are unknown. Using transgenic mouse models of AD together with multiphoton imaging, we measured neuronal calcium in individual neurites and spines in vivo using the genetically encoded calcium indicator Yellow Cameleon 3.6. Quantitative imaging revealed elevated [Ca(2+)]i (calcium overload) in approximately 20% of neurites in APP mice with cortical plaques, compared to less than 5% in wild-type mice, PS1 mutant mice, or young APP mice (animals without cortical plaques). Calcium overload depended on the existence and proximity to plaques. The downstream consequences included the loss of spinodendritic calcium compartmentalization (critical for synaptic integration) and a distortion of neuritic morphologies mediated, in part, by the phosphatase calcineurin. Together, these data demonstrate that senile plaques impair neuritic calcium homeostasis in vivo and result in the structural and functional disruption of neuronal networks.
journal_name
Neuronjournal_title
Neuronauthors
Kuchibhotla KV,Goldman ST,Lattarulo CR,Wu HY,Hyman BT,Bacskai BJdoi
10.1016/j.neuron.2008.06.008subject
Has Abstractpub_date
2008-07-31 00:00:00pages
214-25issue
2eissn
0896-6273issn
1097-4199pii
S0896-6273(08)00501-1journal_volume
59pub_type
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