Amyloid-Beta Levels Fall During Major Depressive Episodes and Rise After Remission

Serum amyloid-beta 42 levels are significantly lower in people aged 60 years and older during acute major depressive episodes. However, these levels return to normal after a 1-year remission period. These are the findings of a study published in Journal of Affective Disorders.

Depression is a known risk factor for Alzheimer disease (AD). It is speculated that changes in amyloid-beta protein metabolism during depressive episodes contribute to the progression of AD.

Researchers conducted a study of 277 older patients with early or late-onset depression admitted to Juntendo Koshigaya Hospital in Saitama, Japan for treatment of a major depressive episode from January 2005 to October 2016. Women were more prevalent than men in the group with major depressive disorder, while the control group had a more balanced representation of the sexes (P <.001).

Researchers analyzed serum levels of amyloid-beta at 3 different time points, including time of admission during the acute depressive episode, immediately after remission, and 1 year after remission. They compared the serum amyloid-beta levels of patients with major depressive disorder with 178 people who did not have depression in the control group.

Compared with the control group, patients with major depressive disorder demonstrated significantly lower serum amyloid-beta 42 levels during an acute depressive episode (P =.001). No changes in this level occurred right away after remission, but serum amyloid-beta 42 levels did increase significantly after 1 year of remission (P <.001).

In contrast, serum levels of amyloid-beta 40 did not differ between the 2 groups — either during the acute episode, immediately after remission, or 1 year after remission.

Since 1 serum level changed while the other remained the same, patients with major depressive disorder had higher amyloid-beta 40/42 ratios — both on admission during the acute episode and immediately after remission (P <.001, respectively). However, after 1 year of remission and following the rise in amyloid-beta 42 levels, this ratio did revert to normal when compared with the control group.

When looking at the 3 time points together, only serum amyloid-beta 42 levels (P =.008) and the amyloid-beta 40/42 ratio (P =.025) changed significantly, while the serum levels of amyloid-beta 40 did not.

“These results suggest that the perturbation in Aβ [amyloid-beta] metabolism caused by depression may ameliorate, although it may require a lengthy period of time after remission,” the researchers stated.

“Our findings also suggest that the risk of developing AD in depressed individuals can be reduced by maintaining remission for an extended period of time.”

Study limitations included the possible influence of antidepressants on the results, the lack of measuring amyloid-beta protein levels within the cerebrospinal fluid (CSF) to correlate serum levels with CSF levels associated with AD, and the gradual drop out of patient enrollment since only 49 patients returned after 1 year of remission.