Evidence map›Paper›PMID 38886798›Full record

ArticleAlzheimer's research & therapy2024

Lower in vivo locus coeruleus integrity is associated with lower cortical thickness in older individuals with elevated Alzheimer's pathology: a cohort study.

Nina Engels-Domínguez, Elouise A Koops, Stephanie Hsieh, Emma E Wiklund, Aaron P Schultz, Joost M Riphagen, Prokopis C Prokopiou, Bernard J Hanseeuw, Dorene M Rentz, Reisa A Sperling and 2 more

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In one paragraph

Article in Alzheimer's research & therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

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0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Nina Engels-DomínguezThe Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02129, USA.
Elouise A KoopsThe Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02129, USA.
Stephanie HsiehThe Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02129, USA.
Emma E WiklundThe Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02129, USA.
Aaron P SchultzThe Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02129, USA.
Joost M RiphagenThe Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02129, USA.
Prokopis C ProkopiouThe Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02129, USA.
Bernard J HanseeuwDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Dorene M RentzDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Reisa A SperlingDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Keith A JohnsonDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Heidi I L JacobsThe Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02129, USA. hjacobs@mgh.harvard.edu.

Funding

Vascular factors, physical activity, and inflammation as modulators of neurodegenerative and cognitive trajectories (Project 2)P01AG036694 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI Rebecca E Amariglio · 2010 to 2026
$50.2M
Project 4P41EB015896 · NIBIB · MASSACHUSETTS GENERAL HOSPITAL · PI ROSEN, BRUCE R · 2012 to 2018
$9.8M
Tracking the origin of tau pathology: dovetailing (pre-)preclinical biomarker trajectoriesR01AG062559 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI Heidi Irma Jacobs · 2019 to 2026
$4.8M
The wandering nerve: gateway to boost Alzheimer's disease related cognitive performanceR01AG068062 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI JACOBS, HEIDI IRMA · 2021 to 2025
$4.6M
Disentangling the contribution of tau to aging and ADR01AG046396 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI JOHNSON, KEITH A. · 2014 to 2018
$4.0M
Postgraduate Training Program in Medical Imaging (PTPMI)T32EB013180 · NIBIB · MASSACHUSETTS GENERAL HOSPITAL · PI Ciprian Catana, Pedram Heidari · 2011 to 2026
$3.7M
Locus coeruleus network architecture of Alzheimer's disease vulnerabilityR01AG082006 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI Heidi Irma Jacobs, Jorge Sepulcre · 2023 to 2026
$2.7M
A Storage Area Network for Structural and Functional Image AnalysisS10RR023401 · NCRR · MASSACHUSETTS GENERAL HOSPITAL · PI FISCHL, BRUCE · 2009 to 2009
$2.0M
SILICON GRAPHICS PRISM EXTREME 128P/1TBS10RR023043 · NCRR · MASSACHUSETTS GENERAL HOSPITAL · PI SORENSEN, ALMA GREGORY · 2006 to 2006
$1.5M
Contribution of locus coeruleus activity patterns on tau deposition in Alzheimer's diseaseR21AG081681 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI PROKOPIOU, PROKOPIS CHRISTOU · 2023 to 2025
$667k
3T MRI for Clinical and Translational ImagingS10OD010364 · OD · MASSACHUSETTS GENERAL HOSPITAL · PI ROSEN, BRUCE R · 2012 to 2012
$600k
A Siemens MAGNETOTOM Trio 3 Tesla MRI SystemS10RR021110 · NCRR · MASSACHUSETTS GENERAL HOSPITAL · PI ROSEN, BRUCE R · 2006 to 2006
$500k
NCRR NIH HHS S10 RR019307NCRR NIH HHS S10 RR021110NCRR NIH HHS S10 RR023043NCRR NIH HHS S10 RR023401NIA NIH HHS P01 AG036694NIA NIH HHS R01 AG046396NIA NIH HHS R01 AG062559NIA NIH HHS R01 AG068062NIA NIH HHS R01 AG082006NIA NIH HHS R21 AG074220NIA NIH HHS R21 AG081681NIA NIH HHS R21 AG082214NIBIB NIH HHS P41 EB015896NIBIB NIH HHS T32 EB013180NIH HHS S10 OD010364NIH HHS S10 OD018035
6 · The paper itself

Abstract

backgroundAutopsy work indicates that the widely-projecting noradrenergic pontine locus coeruleus (LC) is among the earliest regions to accumulate hyperphosphorylated tau, a neuropathological Alzheimer's disease (AD) hallmark. This early tau deposition is accompanied by a reduced density of LC projections and a reduction of norepinephrine's neuroprotective effects, potentially compromising the neuronal integrity of LC's cortical targets. Previous studies suggest that lower magnetic resonance imaging (MRI)-derived LC integrity may signal cortical tissue degeneration in cognitively healthy, older individuals. However, whether these observations are driven by underlying AD pathology remains unknown. To that end, we examined potential effect modifications by cortical beta-amyloid and tau pathology on the association between in vivo LC integrity, as quantified by LC MRI signal intensity, and cortical neurodegeneration, as indexed by cortical thickness.

methodsA total of 165 older individuals (74.24 ± 9.72 years, ~ 60% female, 10% cognitively impaired) underwent whole-brain and dedicated LC 3T-MRI, Pittsburgh Compound-B (PiB, beta-amyloid) and Flortaucipir (FTP, tau) positron emission tomography. Linear regression analyses with bootstrapped standard errors (n = 2000) assessed associations between bilateral cortical thickness and i) LC MRI signal intensity and, ii) LC MRI signal intensity interacted with cortical FTP or PiB (i.e., EC FTP, IT FTP, neocortical PiB) in the entire sample and a low beta-amyloid subsample.

resultsAcross the entire sample, we found a direct effect, where lower LC MRI signal intensity was associated with lower mediolateral temporal cortical thickness. Evaluation of potential effect modifications by FTP or PiB revealed that lower LC MRI signal intensity was related to lower cortical thickness, particularly in individuals with elevated (EC, IT) FTP or (neocortical) PiB. The latter result was present starting from subthreshold PiB values. In low PiB individuals, lower LC MRI signal intensity was related to lower EC cortical thickness in the context of elevated EC FTP.

conclusionsOur findings suggest that LC-related cortical neurodegeneration patterns in older individuals correspond to regions representing early Braak stages and may reflect a combination of LC projection density loss and emergence of cortical AD pathology. This provides a novel understanding that LC-related cortical neurodegeneration may signal downstream consequences of AD-related pathology, rather than being exclusively a result of aging.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesLocus CoeruleusMagnetic Resonance ImagingPositron-Emission Tomographytau ProteinsAgedAged, 80 and overAniline CompoundsBrain Cortical ThicknessCarbolinesCerebral CortexCohort StudiesFemaleHumansMale2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indoleAmyloid beta-PeptidesAniline CompoundsCarbolinestau ProteinsThiazolesAlzheimer’s diseaseBrain structureCortical thicknessFTP-PETLocus coeruleusMRINeurodegenerationPiB-PET

Identifiers

PMID38886798
PMCPMC11181564

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