While there were no significant time-linked associations of Abeta in plasma, there were differences in the CSF.
Overall, both Abeta-40 and -42 in CSF showed a linear increase during waking time, and dips during sleep. The age-matched controls and healthy young subjects – who were presumably amyloid negative – had a steady increase in APP, Abeta-40, and Abeta-42 during waking times. But this finding was absent in subjects with Alzheimer’s.
"In this group, the Abeta-40 increased much less, and the change in Abeta-42 was almost absent," Dr. Huang said.
This suggests that amyloid processing is impaired in patients with the disease. Different enzymes split the APP molecule into the benign Abeta-40, which is secreted into the CSF, and the toxic Abeta-42, which forms brain plaques. A low CSF Abeta-42 level indicates abnormal APP cleavage, leading to retained Abeta-42.
Some studies have suggested that hypoxia alters the enzymatic cleavage of APP, allowing more Abeta-42 production. This finding could have implications in people who experience years of sleep apnea, said Dr. Constantine Lykestos, who moderated the press briefing where the studies were presented.
"There is emerging evidence that hypoxia is associated with amyloidosis, but it’s too new a theory to really know," said Dr. Lykestos, director of the memory and Alzheimer’s treatment center at Johns Hopkins University, Baltimore. "The jury is still out on this relationship."
Dr. Yaffe, Dr. Huang, and Dr. Devore reported no relevant financial disclosures.