Abstract:
:We recently reported that homozygous Presenilin-1 (Psen1) knockin (KI) mice carrying the familial Alzheimer's disease (FAD) mutation L435F or C410Y recapitulate the phenotypes of Psen1(-/-) mice. Production and steady-state levels of Aβ40 and Aβ42 are undetectable in KI/KI brains and reduced in KI/+ brains, though the Aβ42/Aβ40 ratio is slightly increased in KI/+ brains. Moreover, the FAD mutation impairs synaptic function, learning and memory, and age-dependent neuronal survival in the adult brain. Here we extend our analysis of the effects of the L435F and C410Y mutations to the generation of Aβ43. Similar to Aβ40 and Aβ42, production of Aβ43 is undetectable in KI/KI brains and reduced in KI/+ brains. These results support our previous conclusions that the L435F and C410Y mutations cause loss of Presenilin function and γ-secretase activity, including impaired Aβ production in the brain. This Matters Arising Response paper addresses the Veugelen et al. (2016) Matters Arising paper, published concurrently in Neuron.
journal_name
Neuronjournal_title
Neuronauthors
Xia D,Kelleher RJ 3rd,Shen Jdoi
10.1016/j.neuron.2016.03.009subject
Has Abstractpub_date
2016-04-20 00:00:00pages
417-22issue
2eissn
0896-6273issn
1097-4199pii
S0896-6273(16)00209-9journal_volume
90pub_type
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