Epidemiological data have long linked depression with Alzheimer’s disease (AD), a neurodegenerative disease characterized by progressive dementia. however, mechanisms underlying this association remain unclear. Now, a new study identifies common genetic factors in both depression and AD. Importantly, the researchers found that depression played a causal role in AD development, and those with worse depression experienced a faster decline in memory. The study appears in Biological Psychiatry, published by Elsevier.
Co-senior author Aliza Wingo, MD, of Emory University School of Medicine, Atlanta, USA, said of the work:
It raises the possibility that there are genes that contribute to both illnesses. While the shared genetic basis is small, the findings suggest a potential causal role of depression on dementia.
The authors performed a genome-wide association study (GWAS), a technique that scans the entire genome for areas of commonality associated with particular conditions. The GWAS identified 28 brain proteins and 75 transcripts – the messages that encode proteins – that were associated with depression. Among those, 46 transcripts and 7 proteins were also associated with symptoms of AD. The data suggest a shared genetic basis for the two diseases, which may drive the increased risk for AD associated with depression.
Although previous studies had examined AD and depression using GWAS, the current work was made more powerful by using larger, newly available data sets that revealed more detailed information.
Dr. A. Wingo added:
This relationship raises the question of whether treatment of depression can mitigate the risk for dementia. We identified genes that may explain the relationship between depression and dementia here that merit further study. Such genes may be important treatment targets for both depression and reduction of dementia risk.
This does not mean that if one has an episode of depression that dementia is an inevitable result. Instead, it suggests that ineffectively treated depression may aggravate the biology of Alzheimer’s disease, potentially hastening the onset of symptoms and increasing the rate of functional decline.”
For citation: Harerimana NV, Liu Y, Gerasimov ES, Duong D, Beach TG, Reiman EM, Schneider JA, Boyle P, Lori A, Bennett DA, Lah JJ, Levey AI, Seyfried NT, Wingo TS, Wingo AP. Genetic Evidence Supporting a Causal Role of Depression in Alzheimer’s Disease. Biol Psychiatry. 2021 Dec 16:S0006-3223(21)01840-0. doi: 10.1016/j.biopsych.2021.11.025. Epub ahead of print. PMID: 35177243.
