Plasma Amyloid-ß dynamics in late-life major depression: a longitudinal study.

ABSTRACT

Depressed individuals are twice as likely to develop Alzheimer's disease (AD) as compared to controls. Brain amyloid-ß (Aß) deposition is believed to have a major role in AD pathogenesis but studies also suggest associations of Aß dynamics and depression. The aim of this study was to test if plasma Aß levels are longitudinally associated to late-life depression. We measured plasma levels of amyloid-ß1-40 (Aß40) and amyloid-ß1-42 (Aß42) peptides longitudinally for three consecutive years in 48 cognitively intact elderly subjects with late-life major depressive disorder (LLMD) and 45 age-matched cognitively healthy controls. We found that the Aß42/Aß40 plasma ratio was significantly and steadily lower in depressed subjects compared to controls (p < 0.001). At screening, Aß42/Aß40 plasma did not correlate with depression severity (as measured with Hamilton Depression Scale) or cognitive performance (as measured with Mini-Mental State Examination) but was associated to depression severity at 3 years after adjustment for age, education, cognitive performance, and antidepressants use. This study showed that reduced plasma Aß42/Aß40 ratio is consistently associated with LLMD diagnosis and that increased severity of depression at baseline predicted low Aß42/Aß40 ratio at 3 years. Future studies are needed to confirm these findings and examine if the consistently lower plasma Aß42/Aß40 ratio in LLMD reflects increased brain amyloid deposition, as observed in AD subjects, and an increased risk for progressive cognitive decline and AD.