In vivo human molecular neuroimaging of dopaminergic vulnerability along the Alzheimer’s disease phases
Abstract Background Preclinical and pathology evidence suggests an involvement of brain dopamine (DA) circuitry in Alzheimer’s disease (AD). We in vivo investigated if, when, and in which target regions [123I]FP-CIT-SPECT regional binding and molecular connectivity are damaged along the AD course. M...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2021-11-01
|
| Series: | Alzheimer’s Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13195-021-00925-1 |
| _version_ | 1819036671038980096 |
|---|---|
| author | Arianna Sala Silvia Paola Caminiti Luca Presotto Andrea Pilotto Claudio Liguori Agostino Chiaravalloti Valentina Garibotto Giovanni Battista Frisoni Marcello D’Amelio Barbara Paghera Orazio Schillaci Nicola Mercuri Alessandro Padovani Daniela Perani |
| author_facet | Arianna Sala Silvia Paola Caminiti Luca Presotto Andrea Pilotto Claudio Liguori Agostino Chiaravalloti Valentina Garibotto Giovanni Battista Frisoni Marcello D’Amelio Barbara Paghera Orazio Schillaci Nicola Mercuri Alessandro Padovani Daniela Perani |
| author_sort | Arianna Sala |
| collection | DOAJ |
| description | Abstract Background Preclinical and pathology evidence suggests an involvement of brain dopamine (DA) circuitry in Alzheimer’s disease (AD). We in vivo investigated if, when, and in which target regions [123I]FP-CIT-SPECT regional binding and molecular connectivity are damaged along the AD course. Methods We retrospectively selected 16 amyloid-positive subjects with mild cognitive impairment due to AD (AD-MCI), 22 amyloid-positive patients with probable AD dementia (AD-D), and 74 healthy controls, all with available [123I]FP-CIT-SPECT imaging. We tested whether nigrostriatal vs. mesocorticolimbic dopaminergic targets present binding potential loss, via MANCOVA, and alterations in molecular connectivity, via partial correlation analysis. Results were deemed significant at p < 0.05, after Bonferroni correction for multiple comparisons. Results We found significant reductions of [123I]FP-CIT binding in both AD-MCI and AD-D compared to controls. Binding reductions were prominent in the major targets of the ventrotegmental-mesocorticolimbic pathway, namely the ventral striatum and the hippocampus, in both clinical groups, and in the cingulate gyrus, in patients with dementia only. Within the nigrostriatal projections, only the dorsal caudate nucleus showed reduced [123I]FP-CIT binding, in both groups. Molecular connectivity assessment revealed a widespread loss of inter-connections among subcortical and cortical targets of the mesocorticolimbic network only (poor overlap with the control group as expressed by a Dice coefficient ≤ 0.25) and no alterations of the nigrostriatal network (high overlap with controls, Dice coefficient = 1). Conclusion Local- and system-level alterations of the mesocorticolimbic dopaminergic circuitry characterize AD, already in prodromal disease phases. These results might foster new therapeutic strategies for AD. The clinical correlates of these findings deserve to be carefully considered within the emergence of both neuropsychiatric symptoms and cognitive deficits. |
| first_indexed | 2024-12-21T08:09:13Z |
| format | Article |
| id | doaj.art-921d49dd07834f4fb2a6a1ada03cfd92 |
| institution | Directory Open Access Journal |
| issn | 1758-9193 |
| language | English |
| last_indexed | 2024-12-21T08:09:13Z |
| publishDate | 2021-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Alzheimer’s Research & Therapy |
| spelling | doaj.art-921d49dd07834f4fb2a6a1ada03cfd922022-12-21T19:10:42ZengBMCAlzheimer’s Research & Therapy1758-91932021-11-0113111210.1186/s13195-021-00925-1In vivo human molecular neuroimaging of dopaminergic vulnerability along the Alzheimer’s disease phasesArianna Sala0Silvia Paola Caminiti1Luca Presotto2Andrea Pilotto3Claudio Liguori4Agostino Chiaravalloti5Valentina Garibotto6Giovanni Battista Frisoni7Marcello D’Amelio8Barbara Paghera9Orazio Schillaci10Nicola Mercuri11Alessandro Padovani12Daniela Perani13Vita-Salute San Raffaele UniversityVita-Salute San Raffaele UniversityNuclear Medicine Unit, San Raffaele HospitalNeurology Unit, Department of Clinical and Experimental Sciences, University of BresciaDivision of Neurology, Department of Systems Medicine, University of Rome “Tor Vergata”Department of Biomedicine and Prevention, University of Rome “Tor Vergata”Division of Nuclear Medicine and Molecular Imaging, Diagnostic Department, University Hospitals of Geneva, and NIMTLab, Faculty of Medicine, Geneva UniversityDivision of Nuclear Medicine and Molecular Imaging, Diagnostic Department, University Hospitals of Geneva, and NIMTLab, Faculty of Medicine, Geneva UniversityDepartment of Experimental Neurosciences, IRCCS Santa Lucia FoundationNuclear Medicine Unit, Spedali Civili BresciaDepartment of Biomedicine and Prevention, University of Rome “Tor Vergata”Division of Neurology, Department of Systems Medicine, University of Rome “Tor Vergata”Neurology Unit, Department of Clinical and Experimental Sciences, University of BresciaVita-Salute San Raffaele UniversityAbstract Background Preclinical and pathology evidence suggests an involvement of brain dopamine (DA) circuitry in Alzheimer’s disease (AD). We in vivo investigated if, when, and in which target regions [123I]FP-CIT-SPECT regional binding and molecular connectivity are damaged along the AD course. Methods We retrospectively selected 16 amyloid-positive subjects with mild cognitive impairment due to AD (AD-MCI), 22 amyloid-positive patients with probable AD dementia (AD-D), and 74 healthy controls, all with available [123I]FP-CIT-SPECT imaging. We tested whether nigrostriatal vs. mesocorticolimbic dopaminergic targets present binding potential loss, via MANCOVA, and alterations in molecular connectivity, via partial correlation analysis. Results were deemed significant at p < 0.05, after Bonferroni correction for multiple comparisons. Results We found significant reductions of [123I]FP-CIT binding in both AD-MCI and AD-D compared to controls. Binding reductions were prominent in the major targets of the ventrotegmental-mesocorticolimbic pathway, namely the ventral striatum and the hippocampus, in both clinical groups, and in the cingulate gyrus, in patients with dementia only. Within the nigrostriatal projections, only the dorsal caudate nucleus showed reduced [123I]FP-CIT binding, in both groups. Molecular connectivity assessment revealed a widespread loss of inter-connections among subcortical and cortical targets of the mesocorticolimbic network only (poor overlap with the control group as expressed by a Dice coefficient ≤ 0.25) and no alterations of the nigrostriatal network (high overlap with controls, Dice coefficient = 1). Conclusion Local- and system-level alterations of the mesocorticolimbic dopaminergic circuitry characterize AD, already in prodromal disease phases. These results might foster new therapeutic strategies for AD. The clinical correlates of these findings deserve to be carefully considered within the emergence of both neuropsychiatric symptoms and cognitive deficits.https://doi.org/10.1186/s13195-021-00925-1BiomarkerDopamineMolecular connectivitySubstantia nigraVentral tegmental area |
| spellingShingle | Arianna Sala Silvia Paola Caminiti Luca Presotto Andrea Pilotto Claudio Liguori Agostino Chiaravalloti Valentina Garibotto Giovanni Battista Frisoni Marcello D’Amelio Barbara Paghera Orazio Schillaci Nicola Mercuri Alessandro Padovani Daniela Perani In vivo human molecular neuroimaging of dopaminergic vulnerability along the Alzheimer’s disease phases Alzheimer’s Research & Therapy Biomarker Dopamine Molecular connectivity Substantia nigra Ventral tegmental area |
| title | In vivo human molecular neuroimaging of dopaminergic vulnerability along the Alzheimer’s disease phases |
| title_full | In vivo human molecular neuroimaging of dopaminergic vulnerability along the Alzheimer’s disease phases |
| title_fullStr | In vivo human molecular neuroimaging of dopaminergic vulnerability along the Alzheimer’s disease phases |
| title_full_unstemmed | In vivo human molecular neuroimaging of dopaminergic vulnerability along the Alzheimer’s disease phases |
| title_short | In vivo human molecular neuroimaging of dopaminergic vulnerability along the Alzheimer’s disease phases |
| title_sort | in vivo human molecular neuroimaging of dopaminergic vulnerability along the alzheimer s disease phases |
| topic | Biomarker Dopamine Molecular connectivity Substantia nigra Ventral tegmental area |
| url | https://doi.org/10.1186/s13195-021-00925-1 |
| work_keys_str_mv | AT ariannasala invivohumanmolecularneuroimagingofdopaminergicvulnerabilityalongthealzheimersdiseasephases AT silviapaolacaminiti invivohumanmolecularneuroimagingofdopaminergicvulnerabilityalongthealzheimersdiseasephases AT lucapresotto invivohumanmolecularneuroimagingofdopaminergicvulnerabilityalongthealzheimersdiseasephases AT andreapilotto invivohumanmolecularneuroimagingofdopaminergicvulnerabilityalongthealzheimersdiseasephases AT claudioliguori invivohumanmolecularneuroimagingofdopaminergicvulnerabilityalongthealzheimersdiseasephases AT agostinochiaravalloti invivohumanmolecularneuroimagingofdopaminergicvulnerabilityalongthealzheimersdiseasephases AT valentinagaribotto invivohumanmolecularneuroimagingofdopaminergicvulnerabilityalongthealzheimersdiseasephases AT giovannibattistafrisoni invivohumanmolecularneuroimagingofdopaminergicvulnerabilityalongthealzheimersdiseasephases AT marcellodamelio invivohumanmolecularneuroimagingofdopaminergicvulnerabilityalongthealzheimersdiseasephases AT barbarapaghera invivohumanmolecularneuroimagingofdopaminergicvulnerabilityalongthealzheimersdiseasephases AT orazioschillaci invivohumanmolecularneuroimagingofdopaminergicvulnerabilityalongthealzheimersdiseasephases AT nicolamercuri invivohumanmolecularneuroimagingofdopaminergicvulnerabilityalongthealzheimersdiseasephases AT alessandropadovani invivohumanmolecularneuroimagingofdopaminergicvulnerabilityalongthealzheimersdiseasephases AT danielaperani invivohumanmolecularneuroimagingofdopaminergicvulnerabilityalongthealzheimersdiseasephases |