The Neurochemical Landscape of Alzheimer’s Disease.
Alzheimer’s disease (AD) is a devastating neurodegenerative condition that gradually erodes cognitive functions. While extensive research has highlighted the accumulation of toxic proteins like amyloid-β (Aβ) and alterations in brain activity, the intricate relationship between these factors and the brain’s neurochemical systems has remained elusive—until now.
The brain's neurochemical systems refer to networks of chemicals, such as neurotransmitters, that help brain cells perform their functions, such as communicate with each other. Different neurotransmitters, such as dopamine, serotonin, and acetylcholine, play specific roles in regulating mood, memory, attention, and other vital functions. When these systems are disrupted, it can lead to problems with thinking, memory, or mood, which are often seen in conditions like Alzheimer’s disease.
Our latest study, published in open-access by Alzheimer’s & Dementia, aimed to unravel the complex interplay between brain neurochemistry, activity and accumulation of proteins, by examining how changes in brain rhythms and protein deposits align with the how neurochemical systems are distributed across the cortex. The study, performed in collaboration with researchers at the Douglas Mental Health University Institute in Montreal and Boys Town National Research Hospital in Omaha (Nebraska), involved human participants along the Alzheimer’s continuum, from mild cognitive impairment (MCI) to full-blown AD.
Some background
Alzheimer’s disease is marked by the build-up of amyloid-β plaques and tau tangles, which disrupt normal brain activity, particularly in regions critical for memory, attention, and executive function. These disruptions are often expressed as changes in the brain’s rhythmic activity across various frequency bands. Despite recognizing these changes, the field has struggled to understand how they relate to the underlying neurochemical environment of the brain.
Understanding this relationship is crucial because it could open new avenues for early diagnosis and targeted treatments. By investigating this alignment, our study aimed to shed light on how these pathological and physiological changes interact across the Alzheimer’s disease continuum.
Key findings
Using a rare combination of brain imaging techniques, including magnetoencephalography (MEG) and positron emission tomography (PET), we mapped the brain’s neurophysiological changes and amyloid-β deposits in patients with MCI and AD. We then overlaid these maps onto a detailed atlas of 19 neurotransmitter systems to see where these changes occurred most frequently.
Here is what we found:
Alignment with neurochemical systems: We found that disease-related changes in brain rhythms, particularly in the delta (slow) and beta (fast) frequency bands, were closely aligned with specific neurotransmitter systems. For example, alterations in beta rhythms were most pronounced in regions rich in cholinergic receptors—an area of the brain that is particularly vulnerable to the toxic effects of amyloid-β.
Amyloid-β’s role: Amyloid-β deposits were not randomly distributed but instead tended to accumulate along specific neurochemical boundaries. This suggests that the neurochemical environment may influence where and how amyloid-β builds up in the brain, potentially exacerbating the neurophysiological changes observed in AD.
Clinical implications: We found that the strength of these alignments was directly related to the severity of cognitive and behavioral symptoms in patients. This indicates that the more closely these pathological changes align with the brain’s neurochemical systems, the worse the clinical outcomes, such as memory loss or impaired executive function.
Significance
We believe our study provides a new framework for understanding Alzheimer’s disease, emphasizing the role of neurochemical environments in shaping the disease’s progression. By identifying specific neurotransmitter systems that are closely aligned with pathological changes, we open the door to potential new treatments that target these systems to mitigate the effects of Alzheimer’s.
Moreover, our findings suggest that these neurochemical-neurophysiological alignments could serve as biomarkers for early-stage Alzheimer’s, allowing for more accurate diagnosis and personalized treatment strategies before severe symptoms appear.