The authors of this report studied amyloid beta levels in the CSF of elderly subjects with chronic major depression.  These individuals were cognitively intact but were observed to have reductions in CSF amyloid beta 42 similar to individuals with Alzheimer’s disease or mild cognitive impairment. Whether this represents increases in brain amyloid plaque or decreased soluble amyloid beta production was not examined in the current report.

In this report, depressed subjects also showed increased oxidative stress, as measured by levels of F2-isoprostanes in the CSF. Isoprostanes are a product of reactive oxygen species-induced lipid peroxidation and are considered to be biomarkers of oxidative stress. Importantly, amyloid beta 42 levels was found to be inversely correlated with F2-isoprostane levels, suggesting that more oxidative stress was present when levels of amyloid beta 42 were lower. The authors also noted that lower amyloid beta 42 levels were associated with more depressive symptoms.

There was no apparent association between antidepressant treatment and any of the measures tested. The authors suggest that a longitudinal study is warranted to explore whether CSF levels of amyloid beta 42 might change over time in individuals with major depressive disorder and whether the changes are associated with the emergence of progressive cognitive decline or brain structural and functional abnormalities. Unlike subjects with Alzheimer’s disease and mild cognitive impairment, differences in CSF tau protein levels were not observed in individuals with major depression in this study. The development of tau pathology in Alzheimer’s disease is known to be a downstream phenomenon relative to amyloid beta deposition. Whether these individuals might eventually develop increased tau levels, which would be expected in those with prodromal Alzheimer’s disease, requires future study.

Pomara N, Bruno D, Sarreal AS, Hernando RT, Nierenberg J, Petkova E, Sidtis JJ, Wisniewski TM, Mehta PD, Pratico D, Zetterberg H, Blennow K: Lower CSF Amyloid Beta Peptides and Higher F2-Isoprostanes in Cognitively Intact Elderly Individuals With Major Depressive Disorder.  Amer. J. Psychiatry 169(5):523-530 (2012).

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