Amyloid-β oligomers link depressive-like behavior and cognitive deficits in mice

Depression is one of the most common psychiatric symptoms in Alzheimer's disease (AD), and considerable evidence indicates that major depressive disorder increases the risk of AD. [1][2][3] To date, however, the molecular mechanisms underlying the clinical association between depression and AD have remained elusive.Soluble oligomers of the amyloid-b peptide (AbOs) accumulate in the brains of AD patients and are increasingly recognized as the proximal neurotoxins responsible for synapse failure and memory deficits in AD. 4,5 We have hypothesized that AbOs might be mechanistically linked to behavioral changes in AD.In order to test this hypothesis, mice were given a single intracerebroventricular (i.c.v.) injection of 10 pmol AbOs and were subsequently evaluated in the Porsolt forced swim test (FST) for assessment of depressivelike behavior.Compared with vehicle-injected control mice, AbO-injected mice exhibited a significant increase in immobility in the FST, both 24 h and 8 days after AbO injections (Figure 1a).