Journal of the neurological sciences · 2025
Apolipoprotein E genotypes and amyloid burden associated with cognitive decline in non-demented Parkinson's disease patients: A preliminary analysis.
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Trompeta Clara, Gasca-Salas Carmen, Rodríguez-Rojas Rafael, Fernández-Rodríguez Beatriz, Clarimón Jordi, García-Cañamaque Lina, Guida Pasqualina, Hernández-Fernández Frida, Sánchez-Juan Pascual, Olazarán Javier, Vela-Desojo Lydia
Аннотация
BACKGROUND: Cognitive impairment is a common non-motor manifestation in Parkinson's disease (PD). Amyloidosis seems to accelerate the onset of dementia in PD. The Apolipoprotein (APOE) ε4 genotype is linked to amyloid aggregation and has been suggested to be a candidate for development of PD dementia, while other APOE alleles have been less investigated.
METHODS: Forty-eight non-demented PD patients were included (ε2/ε3 carriers: n = 8; ε3/ε3 carriers: n = 35; and ε3/ε4 carriers: n = 5). Patients underwent APOE genotyping, a neuropsychological exam and a [18F]-Flutemetamol PET. Statistical Parametric Mapping 12 was used to analyze regional amyloid differences by APOE genotypes. Cognitive assessment was re-administered after follow-up.
RESULTS: APOE ε3/ε4 carriers showed significant amyloid load in left middle occipital areas in comparison with APOE ε3/ε3, whereas APOE ε3/ε4 exhibited several areas of amyloid accumulation in comparison with APOE ε2/ε3 that disappeared after family-wise error cluster level correction, but which hold in nonparametric analyses. No amyloid load differences were found between APOE ε2/ε3 and APOE ε3/ε3. The frequency of progression of cognitive decline was 80 % in ε3/ε4, 50 % in ε2/ε3, and 22.86 % in ε3/ε3 carriers.
CONCLUSIONS: This compared regional amyloid deposition and cognitive evolution among APOE genotypes. Our preliminary findings suggest an association between APOE ε4 and amyloid burden in posterior cortical areas in non-demented PD and a tendency to a higher frequency of cognitive decline. Larger studies should explore cognition and amyloid burden in APOE ε2 carriers.
METHODS: Forty-eight non-demented PD patients were included (ε2/ε3 carriers: n = 8; ε3/ε3 carriers: n = 35; and ε3/ε4 carriers: n = 5). Patients underwent APOE genotyping, a neuropsychological exam and a [18F]-Flutemetamol PET. Statistical Parametric Mapping 12 was used to analyze regional amyloid differences by APOE genotypes. Cognitive assessment was re-administered after follow-up.
RESULTS: APOE ε3/ε4 carriers showed significant amyloid load in left middle occipital areas in comparison with APOE ε3/ε3, whereas APOE ε3/ε4 exhibited several areas of amyloid accumulation in comparison with APOE ε2/ε3 that disappeared after family-wise error cluster level correction, but which hold in nonparametric analyses. No amyloid load differences were found between APOE ε2/ε3 and APOE ε3/ε3. The frequency of progression of cognitive decline was 80 % in ε3/ε4, 50 % in ε2/ε3, and 22.86 % in ε3/ε3 carriers.
CONCLUSIONS: This compared regional amyloid deposition and cognitive evolution among APOE genotypes. Our preliminary findings suggest an association between APOE ε4 and amyloid burden in posterior cortical areas in non-demented PD and a tendency to a higher frequency of cognitive decline. Larger studies should explore cognition and amyloid burden in APOE ε2 carriers.