Periodic Reporting for period 2 - CONNECT (Connecting neuronal network activity with regional specificity for Alzheimer pathology: a multi-modal neuroimaging approach)
Reporting period: 2019-01-01 to 2019-12-31
Using specific radioactive tracers, Aβ in the brain can be visualized during life. The in vivo visualization of the tau protein is a recent development. This development now allows us to investigate regional interactions among both proteins throughout life.
The overall objectives of this fellowship were intertwined with these recent development as well as with the need to better understand the lifelong biology of this disease in order to halt its progression.
1. To understand the contribution of tau pathology to the relationship between neuronal activity, amyloid deposition and memory performance.
2. To investigate tau pathology of the locus coeruleus using a novel PET tracer and high-field MRI.
3. To determine the “causal” interactions between functional activity (connectivity), amyloid and tau accumulation and memory performance by combining specific PET tracers,(high-field) fMRI with specific statistical modeling
The project has achieved its objectives and milestones with relatively minor deviations (minor delays in publication).
In summary, during this action, the researcher was able to image the locus coeruleus in vivo in humans. The locus coeruleus is a tiny structure in the brainstem and difficult to visualize, but at the same time it is important for Alzheimer’s disease as it is the first site of tau accumulation and modulates various cognitive functions and behaviours. Using these new developed methods, the researcher was able to show that lower integrity of the locus coeruleus was associated with tau accumulation similar to the autopsy staging work. In addition, greater cortical tau accumulation was associated with greater neuronal activity in the locus coeruleus, indicating that the mechanisms underlying the earliest tau propagation may be related to synaptic function and functional connectivity. Finally, the researcher was able to relate changes in locus coeruleus integrity, structurally and functionally, to greater cognitive decline in the context of Alzheimer’s disease, confirming its relevance to both the pathology and symptomatology of Alzheimer’s disease.The results of this projects are ultimately important for our understanding of the pathophysiological cascade of AD and may lead to a new biomarker that could improve the early detection of AD
The researcher’s training aims were: 1) to obtain expertise in Positron Emission Tomography 2) extend statistical knowledge and 3) establish an international network. These objectives were achieved.
The results of this project do contribute to the cumulative conclusion in the field that Alzheimer’s disease is a complex disease, most likely finding its origin early in life and with many biological factors interacting.In addition, these findings suggest that locus coeruleus imaging may be a promising marker of Alzheimer's disease related processes. At a societal level, this is important as the Alzheimer field is moving to earlier intervention, which requires good markers that can predict who is likely to progress.
The researcher has achieved all training objectives, is actively working on transferring knowledge to Europe through workshops with junior researchers, publications and organising a world-wide professional interest area in locus coeruleus imaging. In the Netherlands, she is currently supported by intramural support and Alzheimer Nederland, allowing her to run a large-scale study combining novel MRI-methods with biomarker data.