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FOXP2, APOE, and PRNP: new modulators in primary progressive aphasia
Enrico Premi1, Andrea Pilotto, Antonella Alberici
1Centre for Ageing Brain and Neurodegenerative Disorders, Neurology Unit, University of Brescia, Brescia, Italy.
Journal of Alzheimer'S Disease : JAD
|December 2, 2011
Summary
Genetic variations in FOXP2, APOE, and PRNP influence primary progressive aphasia (PPA) by affecting brain perfusion. APOE ε4 is a significant risk factor for PPA development.
Area of Science:
- Neuroscience
- Genetics
- Neurology
Background:
- Primary progressive aphasia (PPA) is a neurodegenerative disorder causing progressive language decline.
- Genetic factors like FOXP2, APOE, and PRNP are implicated in PPA risk and progression, but with conflicting evidence.
- Understanding these genetic influences is crucial for PPA pathogenesis and therapeutic strategies.
Purpose of the Study:
- To investigate the impact of genetic variations in FOXP2, APOE, and PRNP on PPA.
- To determine if these genetic factors act as risk factors or disease modulators in PPA.
- To correlate genetic profiles with regional brain hypoperfusion in PPA patients.
Main Methods:
- Analysis of FOXP2 polymorphisms (rs1456031, rs17137124), APOE genotype, and PRNP codon 129 status in 94 PPA patients and 200 controls.
- SPECT imaging and Statistical Parametric Mapping (SPM8) analysis in 34 PPA patients.
- Comparison of genetic distributions and regional cerebral blood flow between PPA patients and controls.
Main Results:
- APOE ε4 allele was significantly more frequent in PPA patients compared to controls.
- FOXP2 polymorphisms (rs1456031 and/or rs17137124) correlated with increased frontal hypoperfusion.
- APOE ε4 carriers and PRNP codon 129 homozygotes showed distinct patterns of regional hypoperfusion in orbitofrontal and frontotemporal areas, respectively.
Conclusions:
- Genetic variations in FOXP2, APOE, and PRNP significantly modulate PPA, influencing disease presentation through specific regional hypoperfusion.
- APOE ε4 is identified as an overrepresented genetic risk factor in PPA.
- These findings highlight distinct molecular pathways affected by different genetic variations in PPA.
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