PSEN1 and Alzheimer disease: The declining ratio of Aβ40 to Aβ42 in human biofluids correlates with amyloid accumulation in neural tissue[51] and disease progression.[34, 35] AD patients with Presenilin 1 gene mutations, who exhibit a higher Aβ40 to Aβ42 ratio, experience a later onset of the disease.[52] Studies in mice[53] and Drosophila melanogaster[54] have shown that elevated levels of Aβ40 can mitigate the toxicity induced by Aβ42 and extend lifespan, indicating a protective role for Aβ40.