Epidemiological studies have demonstrated that a history of depression increases the risk of developing dementia, in particular Alzheimer’s disease（AD）. It has been suggested that cerebral vascular changes in elderly depression may be a biological basis for developing dementia. However, the recent large cohort study showed that a history of early-onset depression also increases the risk of developing dementia. On the other hand,recent studies have suggested that an amyloid protein 40（A40）to A42 ratio may be associated with the future onset of AD. Higher plasma A40/A42 ratio have been reported in elderly depression suggesting as a subtype of elderly depression representing a prodromal manifestation of AD. To reveal further relationship between depression and AD, we compared serum A between patients with major depressive disorder（MDD）and healthy controls by age. The result demonstrated that the serum A40/A42 ratio was significantly higher in MDD patients than in controls, and this difference was seen for both elderly and young subjects. This finding may suggests that even young subjects with MDD undergo pathological changes similar to the very early stage of AD, and possibly answer the question of why even early-onset depression is a risk factor for developing AD.