BACKGROUND AND PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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

Canosa A.;Brunetti M.;Barberis M.;Iazzolino B.;Ilardi A.;Cammarosano S.;Manera U.;Moglia C.;Calvo A.;Chio A.
2019

Abstract

BACKGROUND AND PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1468-1331
18; F-2-fluoro-2-deoxy-D-glucose positron emission tomography ; amyotrophic lateral sclerosis; Apolipoprotein E; frontotemporal dementia; Adult; Aged; Alleles; Amyotrophic Lateral Sclerosis; Apolipoproteins E; Brain; Female; Glucose; Humans; Male; Middle Aged; Positron-Emission Tomography; Risk Factors; Genotype
Canosa A.; Pagani M.; Brunetti M.; Barberis M.; Iazzolino B.; Ilardi A.; Cammarosano S.; Manera U.; Moglia C.; Calvo A.; Cistaro A.; Chio A.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/1720178
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