Elevated amyloid beta peptides and total tau in cerebrospinal fluid in individuals with CTD

ACD Summary: In this paper, Rahhal and colleagues investigated three proteins common in Alzheimer’s disease in CTD patients. The link between a lack of creatine in the brain and the neurological symptoms observed in kids with cerebral creatine deficiencies is still not well understood, and this paper looked at one possible explanation. For this study, cerebrospinal fluid (fluid in the brain and spinal cord) was taken from 12 male CTD patients. The fluid was analyzed for the amount of three proteins named tau, Aβ40, and Aβ42. Accumulation of these proteins in the brain is typical in Alzheimer’s disease, and they are believed to be toxic in high amounts. The amounts of these proteins were measured in the CTD patient cerebrospinal fluid samples and were correlated with neurodevelopmental assessment results. The study authors found that CTD patients had elevated levels of all three proteins, compared to individuals without CTD. The amount of protein had an inverse relationship with neurological assessment scores, meaning patients with more of the Alzheimer’s proteins had worse scores. However, patients with seizures had less protein than patients who did not experience seizures. The authors note that due to this surprising result and the small size of the study, these results should be interpreted with caution. They provide a starting point for future research and possible therapeutic targets.

Parent Summary: In this paper, Rahhal and colleagues investigated three proteins common in Alzheimer’s disease in CTD patients. The link between a lack of creatine in the brain and the neurological symptoms observed in kids with cerebral creatine deficiencies is still not well understood, and this paper looked at one possible explanation. For this study, cerebrospinal fluid (fluid in the brain and spinal cord) was taken from 12 male CTD patients. The fluid was analyzed for the amount of three proteins named tau, Aβ40, and Aβ42. Accumulation of these proteins in the brain is typical in Alzheimer’s disease, and they are believed to be toxic in high amounts. The amounts of these proteins were measured in the CTD patient cerebrospinal fluid samples and were correlated with neurodevelopmental assessment results. The study authors found that CTD patients had elevated levels of all three proteins, compared to individuals without CTD. The amount of protein had an inverse relationship with neurological assessment scores, meaning patients with more of the Alzheimer’s proteins had worse scores. However, patients with seizures had less protein than patients who did not experience seizures. The authors note that due to this surprising result and the small size of the study, these results should be interpreted with caution. They provide a starting point for future research and possible therapeutic targets.

See Dr. Rahhal speak about this work in this video from CCDS Day 2024 (3:05:06)

Link to free article: Elevated amyloid beta peptides and total tau in cerebrospinal fluid in individuals with CTD

Authors: Samar Rahhal, Cristan Farmer, Audrey Thurm, Christopher A. Wassif, Niamh X. Cawley, John Perreault, An Dang Do, Simona Bianconi, Fady Hannah-Shmouni, Whitney Guthrie, Laura S. Cubit, Judith S. Miller, V. Reid Sutton, Dwight Koeberl, & Forbes D. Porter

Key Terms: CTD, Clinical study, in vitro, Diagnostic, Mutation study, basic science, pediatric patient, male patient