Cognitive decline in early Alzheimer’s could stem from serotonin loss

MCI patients had 25% lower levels of serotonin compared to healthy patients

Researchers from Johns Hopkins Medicine have suggested that serotonin loss in parts of the brain may play a role in cognitive decline in the early stages of Alzheimer’s disease (AD).

Published in the Journal of Alzheimer’s Disease, the study was supported by other contributing scientists from the Johns Hopkins University School of Medicine and the Johns Hopkins Bloomberg School of Public Health.

Scientists recruited 49 volunteers with mild cognitive impairment (MCI) and 45 healthy adults aged 55 years and older who had previously undergone an MRI to measure changes in brain structure and two positron emission tomography (PET) scans of their brains at Johns Hopkins between 2009 and 2022.

MCI describes the diagnostic stage between normal brain function in ageing and AD.

People living with MCI may stay in their current stage indefinitely or progress to more severe forms of cognitive decline.

Researchers looked specifically at the serotonin transporter, a neurotransmitter that is associated with positive mood, appetite and sleep, to look at the amyloid-beta protein (Aβ) linked with AD.

Previous studies with mice at Johns Hopkins have portrayed how serotonin degeneration can occur before the development of widespread Aβ deposits in the brain.

Most often, a loss of serotonin is associated with depression, anxiety and psychological disorders.

In the study, researchers found that MCI patients had significantly lower levels of serotonin transporter, by up to 25% in the cortical and limbic regions of the brain responsible for executive function, emotion and memory.

Additionally, they found much higher levels of Aβ than health controls in MCI patients.

Gwenn Smith, professor of psychiatry and behavioural sciences, Johns Hopkins University School of Medicine, said: “We may have identified a brain chemical that we can safely target that may improve cognitive deficits and, potentially, depressive symptoms” which could potentially “slow disease progression”.

Researchers intend to follow up on MCI patients in a longitudinal study and are also studying multi-model antidepressant drugs to treat depression and memory deficits to potentially mitigate symptoms.