Non-Fibrillar Oligomeric Amyloid-beta within Synapses
Por:
Pickett, EK, Koffie, RM, Wegmann, S, Henstridge, CM, Herrmann, AG, Colom-Cadena, M, Lleo, A, Kay, KR, Vaught, M, Soberman, R, Walsh, DM, Hyman, BT, Spires-Jones, TL
Publicada:
1 ene 2016
Resumen:
Alzheimer's disease (AD) is characterized by memory loss, insidious cognitive decline, profound neurodegeneration, and the extracellular accumulation of amyloid-beta (A beta) peptide in senile plaques and intracellular accumulation of tau in neurofibrillary tangles. Loss and dysfunction of synapses are believed to underlie the devastating cognitive decline in AD. A large amount of evidence suggests that oligomeric forms of A beta associated with senile plaques are toxic to synapses, but the precise sub-synaptic localization of A beta and which forms are synaptotoxic remain unknown. Here, we characterize the sub-synaptic localization of A beta oligomers using three high-resolution imaging techniques, stochastic optical reconstruction microscopy, immunogold electron microscopy, and Forster resonance energy transfer in a plaque-bearing mouse model of AD. With all three techniques, we observe oligomeric A beta inside synaptic terminals. Further, we tested a panel of A beta antibodies using the relatively high-throughput array tomography technique to determine which forms are present in synapses. Our results show that different oligomeric A beta species are present in synapses and highlight the potential of array tomography for rapid testing of aggregation state specific A beta antibodies in brain tissue.
Filiaciones:
Pickett, EK:
Univ Edinburgh, Ctr Cognit & Neural Syst, Ctr Dementia Prevent, Edinburgh, Midlothian, Scotland
Euan MacDonald Ctr Motor Neurone Dis Res, Edinburgh, Midlothian, Scotland
Koffie, RM:
Massachusetts Gen Hosp, Charlestown, MA USA
Harvard Med Sch, Charlestown, MA USA
Wegmann, S:
Massachusetts Gen Hosp, Charlestown, MA USA
Harvard Med Sch, Charlestown, MA USA
Henstridge, CM:
Univ Edinburgh, Ctr Cognit & Neural Syst, Ctr Dementia Prevent, Edinburgh, Midlothian, Scotland
Euan MacDonald Ctr Motor Neurone Dis Res, Edinburgh, Midlothian, Scotland
Herrmann, AG:
Univ Edinburgh, Ctr Cognit & Neural Syst, Ctr Dementia Prevent, Edinburgh, Midlothian, Scotland
Euan MacDonald Ctr Motor Neurone Dis Res, Edinburgh, Midlothian, Scotland
Colom-Cadena, M:
Univ Autonoma Barcelona, Hosp St Pau, Inst Invest Biomed St Pau, Dept Neurol, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Lleo, A:
Univ Autonoma Barcelona, Hosp St Pau, Inst Invest Biomed St Pau, Dept Neurol, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Kay, KR:
Massachusetts Gen Hosp, Charlestown, MA USA
Harvard Med Sch, Charlestown, MA USA
Vaught, M:
Massachusetts Gen Hosp, Charlestown, MA USA
Harvard Med Sch, Charlestown, MA USA
Soberman, R:
Massachusetts Gen Hosp, Charlestown, MA USA
Harvard Med Sch, Charlestown, MA USA
Walsh, DM:
Brigham & Womens Hosp, Ctr Neurol Dis, Lab Neurodegenerat Res, Boston, MA 02115 USA
Harvard Inst Med, Harvard Med Sch, Boston, MA 02115 USA
Hyman, BT:
Massachusetts Gen Hosp, Charlestown, MA USA
Harvard Med Sch, Charlestown, MA USA
Spires-Jones, TL:
Univ Edinburgh, Ctr Cognit & Neural Syst, Ctr Dementia Prevent, Edinburgh, Midlothian, Scotland
Euan MacDonald Ctr Motor Neurone Dis Res, Edinburgh, Midlothian, Scotland
Green Accepted
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