title: Endogenous amyloid-β is necessary for hippocampal synaptic plasticity and memory.
abstract: OBJECTIVE
  The goal of this study was to investigate the role of endogenous amyloid-β peptide (Aβ) in healthy brain.
  
  
  METHODS
  Long-term potentiation (LTP), a type of synaptic plasticity that is thought to be associated with learning and memory, was examined through extracellular field recordings from the CA1 region of hippocampal slices, whereas behavioral techniques were used to assess contextual fear memory and reference memory. Amyloid precursor protein (APP) expression was reduced through small interfering RNA (siRNA) technique.
  
  
  RESULTS
  We found that both antirodent Aβ antibody and siRNA against murine APP reduced LTP as well as contextual fear memory and reference memory. These effects were rescued by the addition of human Aβ₄₂, suggesting that endogenously produced Aβ is needed for normal LTP and memory. Furthermore, the effect of endogenous Aβ on plasticity and memory was likely due to regulation of transmitter release, activation of α7-containing nicotinic acetylcholine receptors, and Aβ₄₂ production.
  
  
  CONCLUSIONS
  Endogenous Aβ₄₂ is a critical player in synaptic plasticity and memory within the normal central nervous system. This needs to be taken into consideration when designing therapies aiming at reducing Aβ levels to treat Alzheimer disease.
authors.affiliation: Department of Pathology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY 10032, USA.
authors.forename: Daniela
authors.initials: D
authors.lastname: Puzzo
authors.forename: Lucia
authors.initials: L
authors.lastname: Privitera
authors.forename: Mauro
authors.initials: M
authors.lastname: Fa'
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Staniszewski
authors.forename: Gakuji
authors.initials: G
authors.lastname: Hashimoto
authors.forename: Fahad
authors.initials: F
authors.lastname: Aziz
authors.forename: Mikako
authors.initials: M
authors.lastname: Sakurai
authors.forename: Elena M
authors.initials: EM
authors.lastname: Ribe
authors.forename: Carol M
authors.initials: CM
authors.lastname: Troy
authors.forename: Marc
authors.initials: M
authors.lastname: Mercken
authors.forename: Sonia S
authors.initials: SS
authors.lastname: Jung
authors.forename: Agostino
authors.initials: A
authors.lastname: Palmeri
authors.forename: Ottavio
authors.initials: O
authors.lastname: Arancio
mesh_terms: D016229:Amyloid beta-Peptides / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D001703:Biophysics / Q000379:methods; D004558:Electric Stimulation / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005786:Gene Expression Regulation / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000906:Antibodies; D010446:Peptide Fragments; D034741:RNA, Small Interfering; C075222:amyloid beta-protein (1-42)