In a comprehensive study involving over 90 adults, both with and without mild cognitive impairment (MCI), researchers from Johns Hopkins Medicine have observed that individuals with MCI exhibit notably lower serotonin levels — a neurotransmitter often linked to feelings of well-being and happiness — in certain brain regions. This decrease in serotonin levels could potentially contribute to the memory challenges commonly associated with Alzheimer’s disease. Published online on September 13 in the Journal of Alzheimer’s Disease, these findings add to the accumulating evidence that significant changes in brain function may occur early in individuals experiencing mild memory issues, well before an Alzheimer’s diagnosis is confirmed. This research underscores the potential for identifying new therapeutic targets to decelerate or halt the disease’s progression.
The study highlights the early loss of serotonin transporters in individuals with MCI. This condition marks a transitional phase between the expected cognitive decline associated with ageing and the onset of Alzheimer’s disease. Symptoms of MCI include frequent forgetfulness, trouble finding words, and a diminished sense of smell. While some individuals with MCI may not progress beyond this stage, others may develop more severe cognitive impairments, emphasizing the importance of identifying markers that could predict disease progression and potentially guide early intervention strategies.
Gwenn Smith, PhD, a professor of psychiatry and behavioural sciences at the Johns Hopkins University School of Medicine, explains that the research demonstrates a correlation between diminished serotonin transporter levels and memory issues in MCI patients. This correlation persists even when accounting for MRI-detected neurodegeneration and PET-detected amyloid protein levels, both of which are markers associated with Alzheimer’s disease. However, the study’s design does not establish causation or definitively outline serotonin’s role in the transition from MCI to Alzheimer’s disease, signalling the need for further longitudinal studies to explore this relationship.
The research team recruited 49 volunteers with MCI and 45 healthy adults over 55 for the study, which spanned from 2009 to 2022. Participants underwent MRI scans to detect changes in brain structure and two PET scans to examine serotonin transporter levels and the distribution of amyloid-beta (Aβ) protein in the brain. Aβ protein accumulation is a hallmark of Alzheimer’s disease pathology. Previous studies conducted by Johns Hopkins on mice have shown that serotonin degradation precedes the widespread accumulation of beta-amyloid deposits in the brain, linking serotonin loss to depression, anxiety, and other psychological disorders.
The study found that MCI patients had both lower serotonin transporter levels and higher Aβ levels than healthy controls, with up to a 25% reduction in serotonin transporter levels in the cortical and limbic regions of the brain, which are crucial for executive function, emotion, and memory. Smith emphasizes the significance of the correlation between reduced serotonin transporters and memory challenges in MCI, suggesting that targeting this brain chemical could improve cognitive deficits and depressive symptoms. If future research establishes a direct link between serotonin loss and the progression from MCI to Alzheimer’s disease, it could open the door to using newly developed antidepressants as a means to enhance memory and potentially slow the disease’s progression.
Looking ahead, the researchers plan to conduct longitudinal studies to investigate the relationship between serotonin degradation further, increases in Aβ levels, and the accumulation of Tau protein, another Alzheimer’s disease marker, compared to healthy controls. They are also exploring the effectiveness of multi-modal antidepressant drugs in treating depression and memory deficits, with the hope of mitigating and halting the symptoms of Alzheimer’s disease. This collaborative effort involves scientists from the Johns Hopkins University School of Medicine and the Johns Hopkins Bloomberg School of Public Health, highlighting the interdisciplinary approach to understanding and combating Alzheimer’s disease.
More information: Smith, Gwenn S. et al, Serotonin Degeneration and Amyloid-β Deposition in Mild Cognitive Impairment: Relationship to Cognitive Deficits, Journal of Alzheimer’s Disease. DOI: 10.3233/JAD-230570
Journal information: Journal of Alzheimer’s Disease Provided by Johns Hopkins Medicine
