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. INTERPRETATION: 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.
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. INTERPRETATION: 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: J Kang; H G Lemaire; A Unterbeck; J M Salbaum; C L Masters; K H Grzeschik; G Multhaup; K Beyreuther; B Müller-Hill Journal: Nature Date: 1987 Feb 19-25 Impact factor: 49.962
Authors: U Müller; N Cristina; Z W Li; D P Wolfer; H P Lipp; T Rülicke; S Brandner; A Aguzzi; C Weissmann Journal: Cell Date: 1994-12-02 Impact factor: 41.582
Authors: Russell E Nicholls; Jean-Marie Sontag; Hong Zhang; Agnieszka Staniszewski; Shijun Yan; Carla Y Kim; Michael Yim; Caitlin M Woodruff; Erland Arning; Brandi Wasek; Deqi Yin; Teodoro Bottiglieri; Estelle Sontag; Eric R Kandel; Ottavio Arancio Journal: Proc Natl Acad Sci U S A Date: 2016-03-07 Impact factor: 11.205
Authors: Graham Atkin; Jack Hunt; Eiko Minakawa; Lisa Sharkey; Nathan Tipper; William Tennant; Henry L Paulson Journal: J Biol Chem Date: 2014-01-27 Impact factor: 5.157