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Arch Gen Psychiatry. 2008 May;65(5):542-50. doi: 10.1001/archpsyc.65.5.542.

Amyloid-associated depression: a prodromal depression of Alzheimer disease?

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  • 1Department of Psychiatry, Tufts-New England Medical Center, Campus Box 1007, 750 Washington St, Boston, MA 02111, USA.



A high ratio of plasma amyloid-beta peptide 40 (Abeta(40)) to Abeta(42), determined by both high Abeta(40) and low Abeta(42) levels, increases the risk of Alzheimer disease. In a previous study, we reported that depression is also associated with low plasma Abeta(42) levels in the elderly population.


To characterize plasma Abeta(40):Abeta(42) ratio and cognitive function in elderly individuals with and without depression.


Cross-sectional study.


Homecare agencies.


A total of 995 homebound elderly individuals of whom 348 were defined as depressed by a Center for Epidemiological Studies Depression score of 16 or greater.


Cognitive domains of memory, language, executive, and visuospatial functions according to levels of plasma Abeta(40) and Abeta(42) peptides.


Subjects with depression had lower plasma Abeta(42) levels (median, 14.1 vs 19.2 pg/mL; P = .006) and a higher plasma Abeta(40):Abeta(42) ratio (median, 8.9 vs 6.4; P < .001) than did those without depression in the absence of cardiovascular disease and antidepressant use. The interaction between depression and plasma Abeta(40):Abeta(42) ratio was associated with lower memory score (beta = -1.9, SE = 0.7, P = .006) after adjusting for potentially confounders. Relative to those without depression, "amyloid-associated depression," defined by presence of depression and a high plasma Abeta(40):Abeta(42) ratio, was associated with greater impairment in memory, visuospatial ability, and executive function; in contrast, nonamyloid depression was not associated with memory impairment but with other cognitive disabilities.


Amyloid-associated depression may define a subtype of depression representing a prodromal manifestation of Alzheimer disease.

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