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These are uncommon and typically transient

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Dutta, P., Kumar, Y., Babu, A

While the impact of PS mutations on increasing the ratio of 42/40 has been highlighted as a signature of neurodegenerative toxicity [3], a systematic analysis of 138 familial PS mutations in vitro [4] revealed that the 42/40 ratio was not consistently elevated and, more tellingly, 90% of these mutations reduced activity, leading to lower production of A 40 and 42, as observed in several other studies (e.g., [3,4,5,6,7])