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...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Biomarker Dopamine Molecular connectivity Substantia nigra Ventral tegmental area Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/921d49dd07834f4fb2a6a1ada03cfd92
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spelling	oai:doaj.org-article:921d49dd07834f4fb2a6a1ada03cfd922021-11-14T12:39:14ZIn vivo human molecular neuroimaging of dopaminergic vulnerability along the Alzheimer’s disease phases10.1186/s13195-021-00925-11758-9193https://doaj.org/article/921d49dd07834f4fb2a6a1ada03cfd922021-11-01T00:00:00Zhttps://doi.org/10.1186/s13195-021-00925-1https://doaj.org/toc/1758-9193Abstract 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.Arianna SalaSilvia Paola CaminitiLuca PresottoAndrea PilottoClaudio LiguoriAgostino ChiaravallotiValentina GaribottoGiovanni Battista FrisoniMarcello D’AmelioBarbara PagheraOrazio SchillaciNicola MercuriAlessandro PadovaniDaniela PeraniBMCarticleBiomarkerDopamineMolecular connectivitySubstantia nigraVentral tegmental areaNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENAlzheimer’s Research & Therapy, Vol 13, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biomarker Dopamine Molecular connectivity Substantia nigra Ventral tegmental area Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
spellingShingle	Biomarker Dopamine Molecular connectivity Substantia nigra Ventral tegmental area Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 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
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.
format	article
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
title	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_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_sort	in vivo human molecular neuroimaging of dopaminergic vulnerability along the alzheimer’s disease phases
publisher	BMC
publishDate	2021
url	https://doaj.org/article/921d49dd07834f4fb2a6a1ada03cfd92
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In vivo human molecular neuroimaging of dopaminergic vulnerability along the Alzheimer’s disease phases

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