Molecular imaging of the association between serotonin degeneration and beta-amyloid deposition in mild cognitive impairment.

Animals Mice Serotonin Cognitive Dysfunction / metabolism Alzheimer Disease / metabolism Amyloid beta-Peptides / metabolism Positron-Emission Tomography / methods Molecular Imaging

Journal

NeuroImage. Clinical
ISSN: 2213-1582
Titre abrégé: Neuroimage Clin
Pays: Netherlands
ID NLM: 101597070

Informations de publication

Date de publication:
2023
Historique:
received: 01 06 2022
revised: 28 12 2022
accepted: 05 01 2023
pubmed: 22 1 2023
medline: 22 3 2023
entrez: 21 1 2023
Statut: ppublish

Résumé

Degeneration of the serotonin system has been observed in Alzheimer's disease (AD) and in mild cognitive impairment (MCI). In transgenic amyloid mouse models, serotonin degeneration is detected prior to widespread cortical beta-amyloid (Aβ) deposition, also suggesting that serotonin degeneration may be observed in preclinical AD. The differences in the distribution of serotonin degeneration (reflected by the loss of the serotonin transporter, 5-HTT) relative to Aβ deposition was measured with positron emission tomography in a group of individuals with MCI and a group of healthy older adults. A multi-modal partial least squares (mmPLS) algorithm was applied to identify the spatial covariance pattern between 5-HTT availability and Aβ deposition. Forty-five individuals with MCI and 35 healthy older adults were studied, 22 and 27 of whom were included in the analyses who were "amyloid positive" and "amyloid negative", respectively. A pattern of lower cortical, subcortical and limbic 5-HTT availability and higher cortical Aβ deposition distinguished the MCI from the healthy older control participants. Greater expression of this pattern was correlated with greater deficits in memory and executive function in the MCI group, not in the control group. A spatial covariance pattern of lower 5-HTT availability and Aβ deposition was observed to a greater extent in an MCI group relative to a control group and was associated with cognitive impairment in the MCI group. The results support the application of mmPLS to understand the neurochemical changes associated with Aβ deposition in the course of preclinical AD.

Sections du résumé

BACKGROUND
Degeneration of the serotonin system has been observed in Alzheimer's disease (AD) and in mild cognitive impairment (MCI). In transgenic amyloid mouse models, serotonin degeneration is detected prior to widespread cortical beta-amyloid (Aβ) deposition, also suggesting that serotonin degeneration may be observed in preclinical AD.
METHODS
The differences in the distribution of serotonin degeneration (reflected by the loss of the serotonin transporter, 5-HTT) relative to Aβ deposition was measured with positron emission tomography in a group of individuals with MCI and a group of healthy older adults. A multi-modal partial least squares (mmPLS) algorithm was applied to identify the spatial covariance pattern between 5-HTT availability and Aβ deposition.
RESULTS
Forty-five individuals with MCI and 35 healthy older adults were studied, 22 and 27 of whom were included in the analyses who were "amyloid positive" and "amyloid negative", respectively. A pattern of lower cortical, subcortical and limbic 5-HTT availability and higher cortical Aβ deposition distinguished the MCI from the healthy older control participants. Greater expression of this pattern was correlated with greater deficits in memory and executive function in the MCI group, not in the control group.
CONCLUSION
A spatial covariance pattern of lower 5-HTT availability and Aβ deposition was observed to a greater extent in an MCI group relative to a control group and was associated with cognitive impairment in the MCI group. The results support the application of mmPLS to understand the neurochemical changes associated with Aβ deposition in the course of preclinical AD.

Identifiants

DOI: 10.1016/j.nicl.2023.103322 PMID: 36680976 PMC: PMC9869478
pubmed: 36680976
pii: S2213-1582(23)00011-6
doi: 10.1016/j.nicl.2023.103322
pmc: PMC9869478
pii:
doi:

Substances chimiques

Serotonin 333DO1RDJY
Amyloid beta-Peptides 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

103322

Subventions

Organisme : NIA NIH HHS
ID : P30 AG019610
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG072980
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001079
Pays : United States

Informations de copyright

Copyright © 2023. Published by Elsevier Inc.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Auteurs

Gwenn S Smith (GS)

Division of Geriatric Psychiatry and Neuropsychiatry, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Division of Nuclear Medicine and Molecular Imaging, Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: gsmith95@jhmi.edu.

Hillary Protas (H)

Banner Alzheimer's Institute, Phoenix, AZ, USA.

Hiroto Kuwabara (H)

Division of Nuclear Medicine and Molecular Imaging, Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Alena Savonenko (A)

Department of Pathology (Neuropathology), Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Najlla Nassery (N)

Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Neda F Gould (NF)

Division of Geriatric Psychiatry and Neuropsychiatry, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Michael Kraut (M)

Division of Neuroradiology, Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Dimitri Avramopoulos (D)

Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Daniel Holt (D)

Division of Nuclear Medicine and Molecular Imaging, Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Robert F Dannals (RF)

Division of Nuclear Medicine and Molecular Imaging, Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Ayon Nandi (A)

Division of Nuclear Medicine and Molecular Imaging, Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Yi Su (Y)

Banner Alzheimer's Institute, Phoenix, AZ, USA.

Eric M Reiman (EM)

Banner Alzheimer's Institute, Phoenix, AZ, USA.

Kewei Chen (K)

Banner Alzheimer's Institute, Phoenix, AZ, USA.

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Classifications MeSH

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questionsmedicales.fr › Facteurs biologiques › Médiateurs de l'inflammation › Autacoïdes › Sérotonine › Molecular imaging of the association between...
questionsmedicales.fr › Troubles mentaux › Troubles neurocognitifs › Troubles de la cognition › Dysfonctionnement cognitif › Molecular imaging of the association between...
questionsmedicales.fr › Troubles mentaux › Troubles neurocognitifs › Démence › Maladie d'Alzheimer › Molecular imaging of the association between...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Peptides bêta-amyloïdes › Molecular imaging of the association between...
questionsmedicales.fr › Diagnostic › Techniques et procédures diagnostiques › Techniques de diagnostic radioisotopique › Scintigraphie › Tomoscintigraphie › Tomographie par émission de positons › Molecular imaging of the association between...
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