Correlation between Apolipoprotein E genotype and brain metabolism in amyotrophic lateral sclerosis

The aim of the study was to evaluate the metabolic correlates of Apolipoprotein E (APOE) genotype in amyotrophic lateral sclerosis (ALS) and to investigate the role of ε2 as a risk factor for cognitive impairment.

A total of 159 ALS cases underwent APOE and ALS-related genes analysis, neuropsychological assessment and cerebral ¹⁸ F-2-fluoro-2-deoxy-D-glucose positron emission tomography. The APOE genotype was regressed against whole brain metabolism as assessed by ¹⁸ F-2-fluoro-2-deoxy-D-glucose positron emission tomography, with age, sex, education, type of onset and C9orf72 status as covariates.

Brain metabolism was significantly positively correlated with APOE genotype from ε2/ε2 to ε3/ε4 in the left prefrontal [Brodmann area (BA) 10], orbitofrontal (BAs 11, 45, 47) and anterior cingulate (BA 32) cortices. There was a tendency to a relative hypometabolism going towards the ε2/ε2 extreme.

We found a highly significant, relatively lower metabolism in association with the ε2 allele in extra-motor areas typically affected in frontotemporal dementia (left prefrontal, orbitofrontal and anterior cingulate cortices), strengthening the finding of a role of ε2 as a risk factor for cognitive impairment in ALS. Our data suggested a link between cholesterol homeostasis and neurodegeneration.