Different MAPT haplotypes influence expression of total MAPT in postmortem brain tissue.

Area of Science:

• Neuroscience
• Genetics
• Molecular Biology

Background:

• The MAPT gene, encoding tau protein, has two variants (H1 and H2) due to inversion polymorphism.
• Haplotype H1 is linked to increased risk for tauopathies and Parkinson's disease (PD).

Purpose of the Study:

• To investigate if MAPT haplotype influences MAPT and SNCA (α-synuclein) gene expression in PD.
• To explore the role of MAPT variants in gene expression in postmortem brain tissues.

Main Methods:

• MAPT haplotype genotyping in postmortem brain tissues from PD patients and controls.
• Quantification of gene expression using real-time qPCR.
• Analysis of tau and α-synuclein protein levels via Western blotting.

Main Results:

• H1 homozygosity correlated with higher MAPT mRNA in the cortex of the fusiform gyrus (ctx-fg).
• H2 homozygosity was linked to increased MAPT-AS1 expression in the cerebellar hemisphere (ctx-cbl).
• PD patients showed elevated insoluble tau isoforms irrespective of MAPT genotype.

Conclusions:

• Findings suggest a biological relevance of tau in PD, but no direct link between H1/H1 MAPT overexpression and PD status was found.
• Further research is needed on MAPT-AS1's regulatory role and its association with the H2/H2 haplotype in PD.