SAN ANTONIO (June 17, 2021) – Middle-aged people with depressive symptoms who carry a genetic variation called apolipoprotein (APOE) ε4 may be at higher risk of developing buildups of tau protein in areas of the brain that control emotions and memory, one suggests a new study by researchers at the University of Texas at San Antonio Health Sciences Center (UT Health San Antonio) and collaborating institutions.
The Alzheimer’s Disease Journal published the results in its June 2021 print issue. The research is based on assessments of depression and positron emission tomography (PET) imaging of 201 participants in the Framingham Multigenerational Heart Study. The average age of these participants was 53 years old.
Decades before diagnosis
PET scans are typically done in older people, so Framingham’s PET studies in middle-aged people are unique, said Mitzi M. Gonzales, PhD, lead author of the study and neuropsychologist at the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, part of UT Health San Antonio.
“This gives us an interesting opportunity to study people in their 40s and get a feel for factors that might be associated with protein buildups in cognitively normal people,” said Dr Gonzales. “These people are probably decades before any kind of dementia diagnosis, if they are to develop dementia in the future.”
No association found with beta-amyloid
Beta-amyloid (amyloid-β) and tau protein are proteins that aggregate in the brains of people with Alzheimer’s disease and generally increase more moderately with normal aging. The study found no association of depressive symptoms and depression with amyloid-β. The only association was with tau, and only in carriers of the APOE ε4 variant. About a quarter of the participants (47 out of 201) were carriers of 4 because they had at least one copy of the ε4 allele.
Having a copy of APOE ε4 increases the risk of developing Alzheimer’s disease up to two or three times, but some people with this variant live between 80 and 90 years of age and never develop the disease. “It is important to keep in mind that just because a person is identified as a carrier of the APOE ε4 allele does not mean that they will develop dementia in the future,” said Dr Gonzales. “It just means the risk is higher.”
Depressive symptoms (and depression if symptoms were severe enough to reach that diagnostic threshold) were assessed with the Center for Epidemiological Studies Depression Scale at the time of the PET scan, as well as eight years previously. Associations between depressive symptoms and depression with PET results at both time points were assessed, adjusting for age and gender.
Emotion and cognition centers
The study found associations between depressive symptoms and increased tau in two regions of the brain, the entorhinal cortex and the amygdala. “These associations do not imply that the accumulation of tau causes the depressive symptoms, or vice versa,” said Dr. Gonzales. “We only note that both are present in the ε4 carriers.”
The entorhinal cortex is important for memory consolidation and tends to be an area where protein deposition occurs early, she noted. The amygdala, on the other hand, is considered the center of the brain’s emotions.
“Longitudinal studies are needed to better understand what is going on, but it is interesting to reflect on the clinical significance of our findings in terms of cognition as well as emotional regulation,” said Dr Gonzales.
Association of Mid-Life Depressive Symptoms with Regional-β Amyloid and Tau in the Framingham Cardiac Study
Mitzi M. Gonzales, Jasmeet Samra, Adrienne O’Donnell, R. Scott Mackin, Joel Salinas, Mini Jacob, Claudia L. Satizabal, Hugo J. Aparicio, Emma G. Thibault, Justin S. Sanchez, Rebecca Finney, Zoe B. Rubinstein, Danielle V. Mayblyum, Ron J. Killiany, Charlie S. Decarli, Keith A. Johnson, Alexa S. Beiser and Sudha Seshadri
First published: May 15, 2021 (online), Alzheimer’s Disease Journal
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