Variation in TMEM106B in chronic traumatic encephalopathy

Area of Science:

• Neuroscience
• Genetics
• Neuropathology

Background:

• Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease with poorly understood genetic underpinnings.
• Transmembrane protein 106B (TMEM106B) variation is linked to aging neuroinflammation and TDP-43 proteinopathies.
• Neuroinflammation and TDP-43 pathology are key features of CTE.

Purpose of the Study:

• To investigate the association between TMEM106B genetic variation and CTE risk.
• To examine the relationship between TMEM106B variation and CTE pathological features.
• To determine if TMEM106B variation influences ante-mortem dementia in CTE patients.

Main Methods:

• Genotyping of the rs3173615 single nucleotide polymorphism (SNP) in TMEM106B.
• Analysis of 86 deceased male American football players diagnosed with CTE.
• Case-only analysis adjusting for age at death and duration of football play.

Main Results:

• No significant difference in minor allele frequency (MAF) of rs3173615 between CTE cases and controls.
• In CTE cases, the TMEM106B minor allele associated with reduced phosphorylated tau (ptau) and neuroinflammation (CD68) in the dorsolateral frontal cortex.
• The TMEM106B minor allele was linked to increased synaptic protein density and reduced ante-mortem dementia in CTE cases.

Conclusions:

• TMEM106B genetic variation may confer a protective effect against certain CTE-related outcomes.
• The rs3173615 SNP in TMEM106B influences tau pathology, neuroinflammation, and cognitive decline in CTE.
• Further research is warranted to elucidate the role of TMEM106B in CTE pathogenesis.