What is the relationship between depression in middle age and Tau deposition?

According to a new study by researchers at UT Health San Antonio and its partner institutions, middle-aged people with depressive symptoms carry a protein called APOE. Mutations in epsilon 4 May be more likely to produce tau buildup in areas of the brain that control mood and memory.


The Findings were published in the June 2021 print edition of the Journal of Alzheimer's Disease. The Study was based on depression assessments and positron emission tomography (PET) imaging of 201 participants in the multigenerational Framingham Heart Study. The average age of the participants was 53.

The likelihood of finding the disease decades before diagnosis

PET is usually done in older adults, so the Framingham STUDY on PET in middle age is unique, said Mitzi M. Gonzales, the study's lead author and a neuropsychologist at the Glenn Biggs Institute for Alzheimer's disease and Neurodegenerative Diseases, which is part of the University of Texas Health Center at SAN Antonio.

"This gives us an interesting opportunity to study middle-aged people and understand factors that might be associated with the accumulation of protein in cognitively normal people," Dr. Gonzales said. "If these people go on to develop dementia, this study will uncover those possibilities decades before diagnosis."

It has nothing to do with beta-amyloid

Beta-amyloid (Aβ) and Tau are proteins that accumulate in the brains of people with Alzheimer's disease and usually increase gently with age as well. The study found no association between depressive symptoms and depression and beta-amyloid. It was only associated with Tau, and only with carriers of APOE ε4 mutation. About a quarter of the 201 patients (47) carried the ε4 gene because they had at least one ε4 allele.

Carrying one copy of the APOEε4 gene increases the risk of alzheimer's disease by two to three times, but some people who carry the gene variant can live into their 80s or 90s without ever developing the disease. "It is important to remember that just because a person is identified as carrying APOE ε4 does not mean he will develop dementia in the future," Dr. Gonzales said. It just means the stakes are higher."

Depressive symptoms (depression if symptoms are severe enough to meet this diagnostic threshold) were assessed at the time of PET imaging and eight years prior using the Epidemiological Research Center Depression Scale. Depression symptoms and the association between depression and PET outcomes at two time points were assessed, adjusted for age and gender.

Emotional and cognitive centers

The study showed an association between depressive symptoms and an increase in tau in two regions of the brain, the entorhinal cortex and the amygdala. "These associations do not imply that tau accumulation causes depressive symptoms or vice versa," Dr. Gonzales said. "We only noticed these two substances in ε4 carriers."

She noted that the entorhinal cortex is important for memory consolidation and tends to be an area where protein deposition occurs early. Meanwhile, the amygdala is thought to be the emotional center of the brain.

"Longitudinal studies are needed to further understand what's going on, but it's interesting to think about the clinical implications of our findings in terms of cognitive and emotional regulation," Dr. Gonzales said.

Post time: 26-08-21