GRC-MON-PM

Overview of Biomarkers and Genotype-Phenotype Relations

• Discussion on biomarkers focused on fluid imaging & genotype-phenotype connection.

TMEM106B and FTD

• TMEM106B is a major risk factor for Frontotemporal Dementia (FTD).

• T185 risk variant exists alongside a protective variant affecting granulin mutations' disease severity.

• Protective variant reduces disease impact associated with progranulin mutations.

Research Findings on TMEM106B

• Research highlighted increases in core domain amounts in FTD cases.

• Increased core domain correlates with risk factors and genetic variants.

• Suggests endosomal-lysosomal mechanisms linked with TDP-43.

TDP-43 and Disease Mechanisms

• TDP-43 mislocalization leads to splicing consequences.

• Publications indicate TDP-43 loss affects critical gene splicing.

• Criminal events related to cryptic splicing could be developed as biomarkers.

Cryptic Peptides as Potential Biomarkers

• Increased levels of cryptic peptides may indicate loss of TDP-43 function.

• Search for biomarkers is ongoing with a focus on cryptic protein accumulation.

Summary of Clinical Trials and Collaborative Research

• Clinical assessments utilize neurofilament light as a marker for neurodegeneration.

• Various biomarkers like phospho-tau for Alzheimer's are discussed relative to neurodegenerative diseases.

• Biomarker assessments based on plasma measurements can differentiate neurodegenerative from psychiatric conditions.

Future Directions in Research and Biomarker Application

• Continuous refinement of biomarker assays is necessary for differentiating neurodegenerative diseases.

• Genetic mutations in families will be monitored for phenotype predictions.

• Ongoing studies aim to validate the functionality of protective variants in genetic variants.