Science & Society | News | New light at the link between depression and Alzheimer’s disease.

New light at the link between depression and Alzheimer’s disease.

Novel studies from ICVS institute shows that chronic stress precipitates depressive pathology through neurotoxic mechanisms of Alzheimer’s disease

Main findings:

Prolong stressful periods in our life could be causally related to the development of depression, a mental disorder characterized by depressed mood, loss of interest or pleasure low self-worth as well as cognitive deficits that severely damage the individual’s life. More recently, depression is also shown to increase the risk for the development of Alzheimer’s disease (AD), a neurodegenerative disorder that exhibits severe impairments of memory that are progressively followed by drastic changes of personality. However, scientists don’t know yet how these two diseases are linked.

Novel findings in experimental animals from ICVS research team under the guidance of Professor Nuno Sousa (ECS, UMinho) highlight that exposure to chronic stress significantly contributed to the establishment of depressive pathology by activating mechanisms that were previously known to appear/occur in Alzheimer’s disease brain. For mimicking lifetime stress and human depression in experimental animals, researchers often use prolong exposure to different stressful conditions. They found that stress-driven depressive symptomatology in these animals were accompanied by hazardous forms of hyperphosphorylated Tau protein, a characteristic neurotoxic form found in AD brains; note that hyperphosphorylated Tau found in AD patients is known to trigger neuronal malfunction and communication accompanied by loss of communication points between neurons (synapses). When ICVS researchers used experimental animals that lack Tau protein and subsequently, don’t express the AD-related changes under chronic stress, they were able to block the detrimental effects of chronic stress on behavior e.g. depressive behavior, anxiety, lack of pleasure (anhedonia) as well as rescue these animals from the neuronal damage that characterize the disease such as neuronal atrophy, synaptic loss, damaged communication among neurons.


Depression is a common mental disorder that currently affects 350 million people worldwide while clinical evidence supports its connection to the initiation of AD. Interestingly, there is growing consensus that lifetime events such as daily life stressors may increase the probability of risk for both disorders. The present study published in PNAS USA, a leading journal in the field, delivers new insights into the link between stress, depressive pathology and AD demonstrating for the first time that chronic stress triggers the establishment of depressive by using mechanisms that are known to be found in AD.


Providing a novel evidence about the role of Tau and its hyperphosphorylation in brain disorders beyond Alzheimer’s disease, the studies recently published by ICVS research team open a novel “window” of research exploration and opportunities for better understanding of the clinically-suggested connection between the two devastating disorders, depression and Alzheimer’s disease. In addition, these studies provides new light of the neurobiological basis of stress-related neuropsychiatric and neurological disorders highlighting Tau protein as a novel therapeutic target against broader spectrum of brain pathologies.


Professor Nuno Sousa (njcsousa@ecsaude.uminho.pt)


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