sTREM2 is associated with amyloid‐related p‐tau increases and glucose hypermetabolism in Alzheimer's disease
Abstract Microglial activation occurs early in Alzheimer's disease (AD) and previous studies reported both detrimental and protective effects of microglia on AD progression. Here, we used CSF sTREM2 to investigate disease stage‐dependent drivers of microglial activation and to determine downstr...
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Springer Nature
2023-01-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.15252/emmm.202216987 |
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| author | Davina Biel Marc Suárez‐Calvet Paul Hager Anna Rubinski Anna Dewenter Anna Steward Sebastian Roemer Michael Ewers Christian Haass Matthias Brendel Nicolai Franzmeier for the Alzheimer's Disease Neuroimaging Initiative (ADNI) |
| author_facet | Davina Biel Marc Suárez‐Calvet Paul Hager Anna Rubinski Anna Dewenter Anna Steward Sebastian Roemer Michael Ewers Christian Haass Matthias Brendel Nicolai Franzmeier for the Alzheimer's Disease Neuroimaging Initiative (ADNI) |
| author_sort | Davina Biel |
| collection | DOAJ |
| description | Abstract Microglial activation occurs early in Alzheimer's disease (AD) and previous studies reported both detrimental and protective effects of microglia on AD progression. Here, we used CSF sTREM2 to investigate disease stage‐dependent drivers of microglial activation and to determine downstream consequences on AD progression. We included 402 patients with measures of earliest beta‐amyloid (CSF Aβ1‐42) and late‐stage fibrillary Aβ pathology (amyloid‐PET centiloid), as well as sTREM2, p‐tau181, and FDG‐PET. To determine disease stage, we stratified participants into early Aβ‐accumulators (Aβ CSF+/PET−; n = 70) or late Aβ‐accumulators (Aβ CSF+/PET+; n = 201) plus 131 controls. In early Aβ‐accumulators, higher centiloid was associated with cross‐sectional/longitudinal sTREM2 and p‐tau181 increases. Further, higher sTREM2 mediated the association between centiloid and cross‐sectional/longitudinal p‐tau181 increases and higher sTREM2 was associated with FDG‐PET hypermetabolism. In late Aβ‐accumulators, we found no association between centiloid and sTREM2 but a cross‐sectional association between higher sTREM2, higher p‐tau181 and glucose hypometabolism. Our findings suggest that a TREM2‐related microglial response follows earliest Aβ fibrillization, manifests in inflammatory glucose hypermetabolism and may facilitate subsequent p‐tau181 increases in earliest AD. |
| format | Article |
| id | doaj-art-ea66371c81c9496c92efbf79d69b23c9 |
| institution | Kabale University |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2023-01-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-ea66371c81c9496c92efbf79d69b23c92025-08-24T11:43:47ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842023-01-0115211310.15252/emmm.202216987sTREM2 is associated with amyloid‐related p‐tau increases and glucose hypermetabolism in Alzheimer's diseaseDavina Biel0Marc Suárez‐Calvet1Paul Hager2Anna Rubinski3Anna Dewenter4Anna Steward5Sebastian Roemer6Michael Ewers7Christian Haass8Matthias Brendel9Nicolai Franzmeier10for the Alzheimer's Disease Neuroimaging Initiative (ADNI)Institute for Stroke and Dementia Research (ISD), University Hospital, LMU MunichBarcelonaβeta Brain Research Center (BBRC), Pasqual Maragall FoundationInstitute of Radiology and Artificial Intelligence and Informatics in Medicine, TU MunichInstitute for Stroke and Dementia Research (ISD), University Hospital, LMU MunichInstitute for Stroke and Dementia Research (ISD), University Hospital, LMU MunichInstitute for Stroke and Dementia Research (ISD), University Hospital, LMU MunichInstitute for Stroke and Dementia Research (ISD), University Hospital, LMU MunichInstitute for Stroke and Dementia Research (ISD), University Hospital, LMU MunichGerman Center for Neurodegenerative Diseases (DZNE)German Center for Neurodegenerative Diseases (DZNE)Institute for Stroke and Dementia Research (ISD), University Hospital, LMU MunichAbstract Microglial activation occurs early in Alzheimer's disease (AD) and previous studies reported both detrimental and protective effects of microglia on AD progression. Here, we used CSF sTREM2 to investigate disease stage‐dependent drivers of microglial activation and to determine downstream consequences on AD progression. We included 402 patients with measures of earliest beta‐amyloid (CSF Aβ1‐42) and late‐stage fibrillary Aβ pathology (amyloid‐PET centiloid), as well as sTREM2, p‐tau181, and FDG‐PET. To determine disease stage, we stratified participants into early Aβ‐accumulators (Aβ CSF+/PET−; n = 70) or late Aβ‐accumulators (Aβ CSF+/PET+; n = 201) plus 131 controls. In early Aβ‐accumulators, higher centiloid was associated with cross‐sectional/longitudinal sTREM2 and p‐tau181 increases. Further, higher sTREM2 mediated the association between centiloid and cross‐sectional/longitudinal p‐tau181 increases and higher sTREM2 was associated with FDG‐PET hypermetabolism. In late Aβ‐accumulators, we found no association between centiloid and sTREM2 but a cross‐sectional association between higher sTREM2, higher p‐tau181 and glucose hypometabolism. Our findings suggest that a TREM2‐related microglial response follows earliest Aβ fibrillization, manifests in inflammatory glucose hypermetabolism and may facilitate subsequent p‐tau181 increases in earliest AD.https://doi.org/10.15252/emmm.202216987Alzheimer's diseasebeta‐amyloidglucose metabolismp‐tausTREM2 |
| spellingShingle | Davina Biel Marc Suárez‐Calvet Paul Hager Anna Rubinski Anna Dewenter Anna Steward Sebastian Roemer Michael Ewers Christian Haass Matthias Brendel Nicolai Franzmeier for the Alzheimer's Disease Neuroimaging Initiative (ADNI) sTREM2 is associated with amyloid‐related p‐tau increases and glucose hypermetabolism in Alzheimer's disease EMBO Molecular Medicine Alzheimer's disease beta‐amyloid glucose metabolism p‐tau sTREM2 |
| title | sTREM2 is associated with amyloid‐related p‐tau increases and glucose hypermetabolism in Alzheimer's disease |
| title_full | sTREM2 is associated with amyloid‐related p‐tau increases and glucose hypermetabolism in Alzheimer's disease |
| title_fullStr | sTREM2 is associated with amyloid‐related p‐tau increases and glucose hypermetabolism in Alzheimer's disease |
| title_full_unstemmed | sTREM2 is associated with amyloid‐related p‐tau increases and glucose hypermetabolism in Alzheimer's disease |
| title_short | sTREM2 is associated with amyloid‐related p‐tau increases and glucose hypermetabolism in Alzheimer's disease |
| title_sort | strem2 is associated with amyloid related p tau increases and glucose hypermetabolism in alzheimer s disease |
| topic | Alzheimer's disease beta‐amyloid glucose metabolism p‐tau sTREM2 |
| url | https://doi.org/10.15252/emmm.202216987 |
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