Functional gradients of the medial parietal cortex in a healthy cohort with family history of sporadic Alzheimer’s disease
Abstract Background The medial parietal cortex is an early site of pathological protein deposition in Alzheimer’s disease (AD). Previous studies have identified different subregions within this area; however, these subregions are often heterogeneous and disregard individual differences or subtle pat...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-04-01
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| Series: | Alzheimer’s Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13195-023-01228-3 |
| _version_ | 1797841127487832064 |
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| author | Dániel Veréb Mite Mijalkov Yu-Wei Chang Anna Canal-Garcia Emiliano Gomez-Ruis Anne Maass Sylvia Villeneuve Giovanni Volpe Joana B. Pereira |
| author_facet | Dániel Veréb Mite Mijalkov Yu-Wei Chang Anna Canal-Garcia Emiliano Gomez-Ruis Anne Maass Sylvia Villeneuve Giovanni Volpe Joana B. Pereira |
| author_sort | Dániel Veréb |
| collection | DOAJ |
| description | Abstract Background The medial parietal cortex is an early site of pathological protein deposition in Alzheimer’s disease (AD). Previous studies have identified different subregions within this area; however, these subregions are often heterogeneous and disregard individual differences or subtle pathological alterations in the underlying functional architecture. To address this limitation, here we measured the continuous connectivity gradients of the medial parietal cortex and assessed their relationship with cerebrospinal fluid (CSF) biomarkers, ApoE ε4 carriership and memory in asymptomatic individuals at risk to develop AD. Methods Two hundred sixty-three cognitively normal participants with a family history of sporadic AD who underwent resting-state and task-based functional MRI using encoding and retrieval tasks were included from the PREVENT-AD cohort. A novel method for characterizing spatially continuous patterns of functional connectivity was applied to estimate functional gradients in the medial parietal cortex during the resting-state and task-based conditions. This resulted in a set of nine parameters that described the appearance of the gradient across different spatial directions. We performed correlation analyses to assess whether these parameters were associated with CSF biomarkers of phosphorylated tau181 (p-tau), total tau (t-tau), and amyloid-ß1-42 (Aß). Then, we compared the spatial parameters between ApoE ε4 carriers and noncarriers, and evaluated the relationship between these parameters and memory. Results Alterations involving the superior part of the medial parietal cortex, which was connected to regions of the default mode network, were associated with higher p-tau, t-tau levels as well as lower Aß/p-tau levels during the resting-state condition (p < 0.01). Similar alterations were found in ApoE ε4 carriers compared to non-carriers (p < 0.003). In contrast, lower immediate memory scores were associated with changes in the middle part of the medial parietal cortex, which was connected to inferior temporal and posterior parietal regions, during the encoding task (p = 0.001). No results were found when using conventional connectivity measures. Conclusions Functional alterations in the medial parietal gradients are associated with CSF AD biomarkers, ApoE ε4 carriership, and lower memory in an asymptomatic cohort with a family history of sporadic AD, suggesting that functional gradients are sensitive to subtle changes associated with early AD stages. |
| first_indexed | 2024-04-09T16:25:57Z |
| format | Article |
| id | doaj.art-1f07ed18877f40f683c7bbfe7f0aa4f4 |
| institution | Directory Open Access Journal |
| issn | 1758-9193 |
| language | English |
| last_indexed | 2024-04-09T16:25:57Z |
| publishDate | 2023-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Alzheimer’s Research & Therapy |
| spelling | doaj.art-1f07ed18877f40f683c7bbfe7f0aa4f42023-04-23T11:11:09ZengBMCAlzheimer’s Research & Therapy1758-91932023-04-0115111310.1186/s13195-023-01228-3Functional gradients of the medial parietal cortex in a healthy cohort with family history of sporadic Alzheimer’s diseaseDániel Veréb0Mite Mijalkov1Yu-Wei Chang2Anna Canal-Garcia3Emiliano Gomez-Ruis4Anne Maass5Sylvia Villeneuve6Giovanni Volpe7Joana B. Pereira8Department of Neurobiology, Care Sciences and Society, Division of Clinical Geriatrics, Karolinska InstitutetDepartment of Neurobiology, Care Sciences and Society, Division of Clinical Geriatrics, Karolinska InstitutetDepartment of Physics, Goteborg UniversityDepartment of Neurobiology, Care Sciences and Society, Division of Clinical Geriatrics, Karolinska InstitutetDepartment of Physics, Goteborg UniversityGerman Center for Neurodegenerative Diseases (DZNE)Douglas Mental Health University Institute, McGill UniversityDepartment of Physics, Goteborg UniversityDepartment of Neurobiology, Care Sciences and Society, Division of Clinical Geriatrics, Karolinska InstitutetAbstract Background The medial parietal cortex is an early site of pathological protein deposition in Alzheimer’s disease (AD). Previous studies have identified different subregions within this area; however, these subregions are often heterogeneous and disregard individual differences or subtle pathological alterations in the underlying functional architecture. To address this limitation, here we measured the continuous connectivity gradients of the medial parietal cortex and assessed their relationship with cerebrospinal fluid (CSF) biomarkers, ApoE ε4 carriership and memory in asymptomatic individuals at risk to develop AD. Methods Two hundred sixty-three cognitively normal participants with a family history of sporadic AD who underwent resting-state and task-based functional MRI using encoding and retrieval tasks were included from the PREVENT-AD cohort. A novel method for characterizing spatially continuous patterns of functional connectivity was applied to estimate functional gradients in the medial parietal cortex during the resting-state and task-based conditions. This resulted in a set of nine parameters that described the appearance of the gradient across different spatial directions. We performed correlation analyses to assess whether these parameters were associated with CSF biomarkers of phosphorylated tau181 (p-tau), total tau (t-tau), and amyloid-ß1-42 (Aß). Then, we compared the spatial parameters between ApoE ε4 carriers and noncarriers, and evaluated the relationship between these parameters and memory. Results Alterations involving the superior part of the medial parietal cortex, which was connected to regions of the default mode network, were associated with higher p-tau, t-tau levels as well as lower Aß/p-tau levels during the resting-state condition (p < 0.01). Similar alterations were found in ApoE ε4 carriers compared to non-carriers (p < 0.003). In contrast, lower immediate memory scores were associated with changes in the middle part of the medial parietal cortex, which was connected to inferior temporal and posterior parietal regions, during the encoding task (p = 0.001). No results were found when using conventional connectivity measures. Conclusions Functional alterations in the medial parietal gradients are associated with CSF AD biomarkers, ApoE ε4 carriership, and lower memory in an asymptomatic cohort with a family history of sporadic AD, suggesting that functional gradients are sensitive to subtle changes associated with early AD stages.https://doi.org/10.1186/s13195-023-01228-3Alzheimer’s diseaseCognitive agingfMRICerebrospinal fluid markersApolipoprotein EMemory |
| spellingShingle | Dániel Veréb Mite Mijalkov Yu-Wei Chang Anna Canal-Garcia Emiliano Gomez-Ruis Anne Maass Sylvia Villeneuve Giovanni Volpe Joana B. Pereira Functional gradients of the medial parietal cortex in a healthy cohort with family history of sporadic Alzheimer’s disease Alzheimer’s Research & Therapy Alzheimer’s disease Cognitive aging fMRI Cerebrospinal fluid markers Apolipoprotein E Memory |
| title | Functional gradients of the medial parietal cortex in a healthy cohort with family history of sporadic Alzheimer’s disease |
| title_full | Functional gradients of the medial parietal cortex in a healthy cohort with family history of sporadic Alzheimer’s disease |
| title_fullStr | Functional gradients of the medial parietal cortex in a healthy cohort with family history of sporadic Alzheimer’s disease |
| title_full_unstemmed | Functional gradients of the medial parietal cortex in a healthy cohort with family history of sporadic Alzheimer’s disease |
| title_short | Functional gradients of the medial parietal cortex in a healthy cohort with family history of sporadic Alzheimer’s disease |
| title_sort | functional gradients of the medial parietal cortex in a healthy cohort with family history of sporadic alzheimer s disease |
| topic | Alzheimer’s disease Cognitive aging fMRI Cerebrospinal fluid markers Apolipoprotein E Memory |
| url | https://doi.org/10.1186/s13195-023-01228-3 |
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