{"id":232722,"date":"2025-07-14T07:01:36","date_gmt":"2025-07-14T11:01:36","guid":{"rendered":"https:\/\/today.uconn.edu\/?p=232722"},"modified":"2025-07-21T14:33:21","modified_gmt":"2025-07-21T18:33:21","slug":"demystifying-the-link-between-major-depression-and-alzheimers-disease","status":"publish","type":"post","link":"https:\/\/today.uconn.edu\/2025\/07\/demystifying-the-link-between-major-depression-and-alzheimers-disease\/","title":{"rendered":"Demystifying the Link Between Major Depression and Alzheimer\u2019s Disease"},"content":{"rendered":"

Over 7 million people in the United States live with Alzheimer\u2019s disease and related dementia (ADRD). Some risk factors for ADRD, like genetics, can\u2019t be controlled, but others can be treated. One of the most prevalent is depression (known clinically as major depressive disorder, or MDD). Between 11.1% and 14.7% of ADRD cases<\/a> \u2013 affecting roughly one million individuals in the US \u2013 are attributable to MDD. <\/span>\u00a0<\/span><\/p>\n

Now, researchers at the <\/span>UConn Center on Aging<\/span><\/a> have uncovered a variety of mechanisms linking these conditions, giving at-risk individuals and health care providers a greater understanding of how the disease may be prevented and mitigated.<\/span>\u00a0<\/span><\/p>\n

\u201cWe\u2019ve known for a long time that depression is one of the most relevant, potentially preventable risk factors for Alzheimer\u2019s disease,\u201d says Breno Diniz, MD, Ph.D., associate professor of psychiatry at UConn Health and the Center on Aging, who has devoted his research career to tackling this issue. \u201cHowever, we didn\u2019t know why.\u201d<\/span> \u00a0<\/span><\/p>\n

Diniz’s latest publication<\/a>, in the journal Nature Mental Health, has uncovered two key factors linking these diseases: proteostasis<\/span>,<\/span><\/i> or how the body synthesizes and metabolizes proteins; and dysregulation of inflammatory responses. <\/span>\u00a0<\/span><\/p>\n

\u201cDepression is a disease that is bigger than a depressed mood,\u201d Diniz says. \u201cIt has consequences that are silent, that may appear many years later.\u201d<\/span>\u00a0<\/span><\/p>\n

The Power in the Proteins<\/h2>\n

Diniz\u2019s research team identified a series of protein markers in the body that seemed to increase the risk of ADRD for everyone \u2013 patients both with and without a history of MDD. These markers are related to general processes in the body that tend to change with age, such as inflammation, cell division, and apoptosis (the destruction and removal of damaged cells from the body).<\/span>\u00a0<\/span><\/p>\n

But in patients with MDD, the researchers found a unique change in the process of proteostasis. This change increased inflammation in the brain, which in turn increased the risk of developing ADRD.<\/span>\u00a0<\/span><\/p>\n

\u201cWhat we have here is a causal effect,\u201d says Diniz, explaining that these two factors \u2013 changes in proteostasis and an increase in neuroinflammation\u00a0\u2013\u00a0\u201cseem to work together, synergistically, to increase the risk of dementia.\u201d<\/span>\u00a0<\/span><\/p>\n

Using this insight, the team developed a Proteomic Risk Score that can be used to assess the risk for an individual patient with depression developing ADRD. This unique tool evaluates multiple proteins and offers \u201ca more concrete way of looking at the risk of dementia in these individuals,\u201d says Diniz.<\/span>\u00a0<\/span><\/p>\n

To the research team’s surprise, the newly developed tool was a better predictor of ADRD risk than any previous model. It was more effective than models which evaluate the classic risk factors for ADRD, both in the general population and among those with depression \u2013 signaling hope for early detection and prevention.<\/span>\u00a0<\/span><\/p>\n

\u201cIt\u2019s a very robust model,\u201d says Diniz, \u201cand it has concrete clinical applications.\u201d<\/span>\u00a0<\/span><\/p>\n

The Proteomic Risk Score tool will help clinicians and patients holistically examine their ADRD risk factors, and it may also enable researchers to better select human subjects for ADRD intervention and prevention efforts.<\/span>\u00a0<\/span><\/p>\n

Breaking it Down<\/h2>\n

In this study, Diniz and his co-authors used a combination of proteomic and genomic approaches to analyze data available from the United Kingdom Biobank, specifically tracking ADRD outcomes among middle-aged adults with depression. <\/span>\u00a0<\/span><\/p>\n

Proteomics is the study of the proteins that are created by cells in the body. And genomics \u2013 the study of someone\u2019s entire set of DNA \u2013 is a natural complement to proteomics, since DNA determines which proteins are produced by cells. Combining these two analytical approaches is called proteogenomics, and it can give researchers a deeper insight into complex biological processes and how they are related to different pathologies. <\/span>\u00a0<\/span><\/p>\n

\u201cEvery molecular layer \u2013 from genes to epigenetics, RNA, and proteins \u2013 conveys different biological information, and they can have different roles in … creating prediction models,\u201d explains Diniz. \u201cTheir combination makes the models more powerful, and brings them a step closer to precision geroscience.\u201d This is a major goal of the <\/span>UConn Pepper Center<\/span><\/a>, led by the paper\u2019s co-authors George Kuchel, MD, and Richard Fortinsky, Ph.D.<\/span><\/p>\n

To enable this multifaceted analysis, Diniz partnered with other researchers across departments at UConn and UConn Health, including Kuchel; Fortinsky; Zhiduo Chen, Ph.D.; David C. Steffens, MD; and Chia-Ling Kuo, Ph.D. The research team also included scientists from the University of Exeter (UK) and the Centre for Addiction and Mental Health in Toronto, Canada.<\/span>\u00a0<\/span><\/p>\n

Depression\u2019s \u2018Silent Consequences\u2019<\/h2>\n

This research emphasizes the profound interconnection between mind and body, especially the long-term health impacts of untreated mental illness. For those outside the scientific community, Diniz hopes this work will spur people to take their mental health just as seriously as their physical health.<\/span>\u00a0<\/span><\/p>\n

\u201cIt\u2019s extremely important to seek help,” Diniz urges. \u201cNot only when you\u2019re 50 or older \u2013 anytime in your life. Lots of studies in the past decade have shown that any depressive episode throughout the lifespan, even in your 20s, can increase the risk of dementia later on. So, it\u2019s very important to seek help, and it\u2019s very important to treat \u2013 and try to reach full remission of \u2013 the depressive episode.\u201d<\/span>\u00a0<\/span><\/p>\n

Fortunately, he notes, many of the lifestyle recommendations which have been shown to improve depressive symptoms \u2013 like exercise and not smoking \u2013 also improve other health outcomes, so treating depression does not need to occur in isolation.<\/span>\u00a0<\/span><\/p>\n

Offering patients and health care providers tools like the Proteomic Risk Score and a more holistic understanding of health, this research joins a growing body of literature dedicated to preventing many cases of ADRD before it\u2019s too late.<\/span>\u00a0<\/span><\/p>\n

 <\/p>\n

This work was supported by the NIA grant P30AG067988 (UConn Pepper Center, PIs: Kuchel and Fortinsky). <\/span><\/i>\u00a0<\/span><\/p>\n","protected":false},"excerpt":{"rendered":"

UConn investigators uncover new risk factors linking depression and dementia<\/p>\n","protected":false},"author":175,"featured_media":232748,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_crdt_document":"","wds_primary_category":0,"wds_primary_series":0,"wds_primary_attribution":0,"footnotes":""},"categories":[2283,2460,2231,2648,2076,1868,2235,179],"tags":[],"magazine-issues":[],"coauthors":[2413],"class_list":["post-232722","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-aging","category-faculty","category-health-well-being","category-blue-research","category-research","category-meds","category-today-homepage","category-uconn-health"],"pp_statuses_selecting_workflow":false,"pp_workflow_action":"current","pp_status_selection":"publish","acf":[],"publishpress_future_action":{"enabled":false,"date":"2026-06-02 22:30:47","action":"change-status","newStatus":"draft","terms":[],"taxonomy":"category","extraData":[]},"publishpress_future_workflow_manual_trigger":{"enabledWorkflows":[]},"_links":{"self":[{"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/posts\/232722","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/users\/175"}],"replies":[{"embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/comments?post=232722"}],"version-history":[{"count":7,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/posts\/232722\/revisions"}],"predecessor-version":[{"id":232771,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/posts\/232722\/revisions\/232771"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/media\/232748"}],"wp:attachment":[{"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/media?parent=232722"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/categories?post=232722"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/tags?post=232722"},{"taxonomy":"magazine-issue","embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/magazine-issues?post=232722"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/coauthors?post=232722"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}