The MITGEST online DC Forum recently welcomed Dr. Llwyd Prosser, research fellow in Neuroimaging at the Dementia Research Centre, University College London, for an engaging and forward-thinking presentation on his academic background, distinctive research approach and also his latest work. His research focuses on identifying early biological markers that predict cognitive decline, with a particular emphasis on Alzheimer’s disease (AD), cerebrovascular changes, and neurodegeneration.
Multi-factor Predictive Models of Cognitive Decline
Dr. Prosser shared two of his most recent studies that investigate the complexity of imaging markers and disease progression. The first, “Predicting Cognitive Decline in Older Adults Using Baseline Metrics of AD Pathologies, Cerebrovascular Disease, and Neurodegeneration,” demonstrates how a combination of baseline brain imaging and fluid markers, including amyloid-beta accumulation, tau pathology, vascular burden, and brain volumes can improve identification of later diagnostic progression . His findings support a multi-factor model of risk, where no single biomarker tells the full story.
Challenging the Binary: Amyloid Positivity Reconsidered
The second paper, “Biomarker Heterogeneity of Those Amyloid Positive,” explores why individuals with abnormal amyloid deposition can have widely different clinical outcomes. Through subtype and Stage Inference (SuStaIn), Dr. Prosser found that people who are amyloid-positive actually represent biologically diverse subgroups, differing in tau load, neurodegeneration, and vascular burden. These findings challenge the current binary view of “amyloid positive or negative” and advocate for a more refined, personalised approach.
The Mitochondrial Perspective: A Hidden Driver?
For our network, which focuses on mitochondrial biology and dysfunction, Dr. Prosser’s work opens an exciting translational avenue. Mitochondrial impairment has long been implicated in both neurodegenerative disease and vascular dysfunction. In fact, mitochondrial stress and altered bioenergetics may be upstream contributors to the biomarkers Dr. Prosser studies, such as brain atrophy, white matter damage, and even abnormal amyloid and tau processing.
As Dr. Prosser emphasised, predicting cognitive decline requires a systems-level understanding of interacting pathologies. This is where the mitochondrial perspective is especially valuable. Mitochondria lie at the crossroads of metabolic regulation, oxidative stress, and cell survival, and their dysfunction may be a common thread linking vascular injury, protein aggregation, and neuronal loss.
Looking Ahead: Integration and Collaboration
MITGEST researchers are uniquely positioned to integrate mitochondrial biomarkers into these emerging multi-modal models of cognitive risk. Collaborations that combine imaging data with mitochondrial profiling could help illuminate hidden drivers of heterogeneity within the ageing brain.
Dr. Prosser’s presentation not only enriched our understanding of how neuroimaging and biomarker study can advance cognitive ageing research, but also showed how mitochondrial biology could enhance these models. The integration of mitochondrial health markers into neurodegenerative risk models could deliver powerful diagnostic opportunities.
We thank Dr. Prosser for his valuable contributions and look forward to building cross-disciplinary collaborations that bridge neuroimaging, pathology, and mitochondrial research.
The news item was written by MITGEST DC7 Seungtae Lee.
Share the news:
