The prion protein as a receptor for amyloid-β

• Published in: Nature (London) Vol. 466; no. 7308; pp. E3 - E4
• Main Authors: Kessels, Helmut W., Nguyen, Louis N., Nabavi, Sadegh, Malinow, Roberto
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.08.2010; Nature Publishing Group
• Subjects: 631/378/1689/1414; 631/378/2591; 631/45/460; 692/699/375/365/1283; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Amyloid beta-Peptides - chemistry; Amyloid beta-Peptides - genetics; Amyloid beta-Peptides - metabolism; Amyloid beta-protein; Animals; brief-communications-arising; Health aspects; Humanities and Social Sciences; Learning - physiology; Long-term potentiation; Mice; Mice, Inbred C57BL; Mice, Transgenic; multidisciplinary; Physiological aspects; Prions; PrPC Proteins - deficiency; PrPC Proteins - genetics; PrPC Proteins - metabolism; Reproducibility of Results; Risk factors; Science; Science (multidisciplinary); Serotonin - metabolism; Synapses - metabolism; Synapses - pathology; Synaptic Transmission; United States
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature09217

Arising from: J. Laurén et al. Nature457, 1128–1132 (2009)10.1038/nature07761 ; Laurén et al. reply Increased levels of brain amyloid-β, a secreted peptide cleavage product of amyloid precursor protein (APP), is believed to be critical in the aetiology of Alzheimer’s disease 1 . Increased amyloid-β can cause synaptic depression 2 , 3 , reduce the number of spine protrusions (that is, sites of synaptic contacts) 4 , 5 and block long-term synaptic potentiation (LTP) 6 , 7 , a form of synaptic plasticity; however, the receptor through which amyloid-β produces these synaptic perturbations has remained elusive. Laurén et al. 8 suggested that binding between oligomeric amyloid-β (a form of amyloid-β thought to be most active 5 , 6 , 9 , 10 , 11 ) and the cellular prion protein (PrP C ) 8 is necessary for synaptic perturbations. Here we show that PrP C is not required for amyloid-β-induced synaptic depression, reduction in spine density, or blockade of LTP; our results indicate that amyloid-β-mediated synaptic defects do not require PrP c .