Respective influence of beta-amyloid and APOE ε4 genotype on medial temporal lobe subregions in cognitively unimpaired older adults
Medial temporal lobe (MTL) subregions are differentially affected in Alzheimer's disease (AD), with a specific involvement of the entorhinal cortex (ERC), perirhinal cortex and hippocampal cornu ammonis (CA)1. While amyloid (Aβ) and APOEε4 are respectively the first molecular change and the mai...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-06-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996123001419 |
| _version_ | 1797827785164587008 |
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| author | Robin de Flores Solène Demeilliez-Servouin Elizabeth Kuhn Léa Chauveau Brigitte Landeau Nicolas Delcroix Julie Gonneaud Denis Vivien Gaël Chételat |
| author_facet | Robin de Flores Solène Demeilliez-Servouin Elizabeth Kuhn Léa Chauveau Brigitte Landeau Nicolas Delcroix Julie Gonneaud Denis Vivien Gaël Chételat |
| author_sort | Robin de Flores |
| collection | DOAJ |
| description | Medial temporal lobe (MTL) subregions are differentially affected in Alzheimer's disease (AD), with a specific involvement of the entorhinal cortex (ERC), perirhinal cortex and hippocampal cornu ammonis (CA)1. While amyloid (Aβ) and APOEε4 are respectively the first molecular change and the main genetic risk factor in AD, their links with MTL atrophy remain relatively unclear.Our aim was to uncover these effects using baseline data from 130 participants included in the Age-Well study, for whom ultra-high-resolution structural MRI, amyloid-PET and APOEε4 genotype were available.No volume differences were observed between Aβ + (n = 24) and Aβ- (n = 103), nor between APOE4+ (n = 35) and APOE4- (n = 95) participants. However, our analyses showed that both Aβ and APOEε4 status interacted with age on CA1, which is known to be specifically atrophied in early AD. In addition, APOEε4 status moderated the effects of age on other subregions (subiculum, ERC), suggesting a more important contribution of APOEε4 than Aβ to MTL atrophy in cognitively unimpaired population.These results are crucial to develop MRI-based biomarkers to detect early AD. |
| first_indexed | 2024-04-09T12:53:54Z |
| format | Article |
| id | doaj.art-8ac69674baeb45679f810d0312883164 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-04-09T12:53:54Z |
| publishDate | 2023-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-8ac69674baeb45679f810d03128831642023-05-14T04:28:12ZengElsevierNeurobiology of Disease1095-953X2023-06-01181106127Respective influence of beta-amyloid and APOE ε4 genotype on medial temporal lobe subregions in cognitively unimpaired older adultsRobin de Flores0Solène Demeilliez-Servouin1Elizabeth Kuhn2Léa Chauveau3Brigitte Landeau4Nicolas Delcroix5Julie Gonneaud6Denis Vivien7Gaël Chételat8INSERM UMR-S U1237, PhIND “Physiopathology and Imaging of Neurological Disorders”, Institut Blood and Brain @ Caen-Normandie, Caen-Normandie University, GIP Cyceron, France; Corresponding author at: Inserm U1237-PhIND, GIP Cyceron, Bd Henri Becquerel, BP 5229, 14074, Caen cedex 5, France.INSERM UMR-S U1237, PhIND “Physiopathology and Imaging of Neurological Disorders”, Institut Blood and Brain @ Caen-Normandie, Caen-Normandie University, GIP Cyceron, FranceINSERM UMR-S U1237, PhIND “Physiopathology and Imaging of Neurological Disorders”, Institut Blood and Brain @ Caen-Normandie, Caen-Normandie University, GIP Cyceron, FranceINSERM UMR-S U1237, PhIND “Physiopathology and Imaging of Neurological Disorders”, Institut Blood and Brain @ Caen-Normandie, Caen-Normandie University, GIP Cyceron, FranceINSERM UMR-S U1237, PhIND “Physiopathology and Imaging of Neurological Disorders”, Institut Blood and Brain @ Caen-Normandie, Caen-Normandie University, GIP Cyceron, FranceCNRS UMS 3408, GIP Cyceron, FranceINSERM UMR-S U1237, PhIND “Physiopathology and Imaging of Neurological Disorders”, Institut Blood and Brain @ Caen-Normandie, Caen-Normandie University, GIP Cyceron, FranceINSERM UMR-S U1237, PhIND “Physiopathology and Imaging of Neurological Disorders”, Institut Blood and Brain @ Caen-Normandie, Caen-Normandie University, GIP Cyceron, FranceINSERM UMR-S U1237, PhIND “Physiopathology and Imaging of Neurological Disorders”, Institut Blood and Brain @ Caen-Normandie, Caen-Normandie University, GIP Cyceron, FranceMedial temporal lobe (MTL) subregions are differentially affected in Alzheimer's disease (AD), with a specific involvement of the entorhinal cortex (ERC), perirhinal cortex and hippocampal cornu ammonis (CA)1. While amyloid (Aβ) and APOEε4 are respectively the first molecular change and the main genetic risk factor in AD, their links with MTL atrophy remain relatively unclear.Our aim was to uncover these effects using baseline data from 130 participants included in the Age-Well study, for whom ultra-high-resolution structural MRI, amyloid-PET and APOEε4 genotype were available.No volume differences were observed between Aβ + (n = 24) and Aβ- (n = 103), nor between APOE4+ (n = 35) and APOE4- (n = 95) participants. However, our analyses showed that both Aβ and APOEε4 status interacted with age on CA1, which is known to be specifically atrophied in early AD. In addition, APOEε4 status moderated the effects of age on other subregions (subiculum, ERC), suggesting a more important contribution of APOEε4 than Aβ to MTL atrophy in cognitively unimpaired population.These results are crucial to develop MRI-based biomarkers to detect early AD.http://www.sciencedirect.com/science/article/pii/S0969996123001419Medial temporal lobeHippocampal subfieldsAmyloidAPOEAlzheimer's diseaseAge |
| spellingShingle | Robin de Flores Solène Demeilliez-Servouin Elizabeth Kuhn Léa Chauveau Brigitte Landeau Nicolas Delcroix Julie Gonneaud Denis Vivien Gaël Chételat Respective influence of beta-amyloid and APOE ε4 genotype on medial temporal lobe subregions in cognitively unimpaired older adults Neurobiology of Disease Medial temporal lobe Hippocampal subfields Amyloid APOE Alzheimer's disease Age |
| title | Respective influence of beta-amyloid and APOE ε4 genotype on medial temporal lobe subregions in cognitively unimpaired older adults |
| title_full | Respective influence of beta-amyloid and APOE ε4 genotype on medial temporal lobe subregions in cognitively unimpaired older adults |
| title_fullStr | Respective influence of beta-amyloid and APOE ε4 genotype on medial temporal lobe subregions in cognitively unimpaired older adults |
| title_full_unstemmed | Respective influence of beta-amyloid and APOE ε4 genotype on medial temporal lobe subregions in cognitively unimpaired older adults |
| title_short | Respective influence of beta-amyloid and APOE ε4 genotype on medial temporal lobe subregions in cognitively unimpaired older adults |
| title_sort | respective influence of beta amyloid and apoe ε4 genotype on medial temporal lobe subregions in cognitively unimpaired older adults |
| topic | Medial temporal lobe Hippocampal subfields Amyloid APOE Alzheimer's disease Age |
| url | http://www.sciencedirect.com/science/article/pii/S0969996123001419 |
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