The normal equilibrium between CSF and plasma amyloid beta levels is disrupted in Alzheimer's disease

Amyloid-beta (Aβ) with 40 (Aβ40) and 42 (Aβ42) amino acids, the main components of amyloid plaques in the Alzheimer's disease (AD) brain, can be measured in human cerebrospinal fluid (CSF) and plasma. Whereas CSF Aβ42 is decreased in AD, some studies have reported changed plasma Aβ levels in AD and in subjects with mild cognitive impairment (MCI). To this date it is unclear if and how CSF and plasma levels of Aβ correlate with each other in healthy individuals, albeit earlier studies on AD patients found no correlation between CSF and plasma Aβ. We have measured Aβ40 and Aβ42 in paired CSF and plasma samples from patients with AD (n = 39), MCI (n = 29) and healthy control subjects (n = 18). We observed a clear correlation between CSF and plasma levels for both Aβ40 and Aβ42 in healthy individuals, whereas no such correlation could be seen for AD or MCI cases. Similarly to other studies we also found low levels of Aβ42 in AD CSF, whereas there were no significant differences in plasma Aβ levels between the diagnostic groups. Our findings suggest that the normal equilibrium between CSF and plasma Aβ may be disrupted with the initiation of amyloid deposition in the brain.