Spatiotemporal patterns of locus coeruleus integrity predict cortical tau and cognition

Elisenda Bueichekú; Ibai Diez; Chan-Mi Kim; John Alex Becker; Elouise A Koops; Kenneth Kwong; Kathryn V Papp; David H Salat; David A Bennett; Dorene M Rentz; Reisa A Sperling; Keith A Johnson; Jorge Sepulcre; Heidi I L Jacobs

doi:10.1038/s43587-024-00626-y

Spatiotemporal patterns of locus coeruleus integrity predict cortical tau and cognition

Elisenda Bueichekú, Ibai Diez, Chan-Mi Kim, John Alex Becker, Elouise A Koops, Kenneth Kwong, Kathryn V Papp, David H Salat, David A Bennett, Dorene M Rentz, Reisa A Sperling, Keith A Johnson, Jorge Sepulcre^*, Heidi I L Jacobs^*

^*Corresponding author for this work

Research output: Contribution to journal › Comment/Letter to the editor › Academic › peer-review

Abstract

Autopsy studies indicated that the locus coeruleus (LC) accumulates hyperphosphorylated tau before allocortical regions in Alzheimer's disease. By combining in vivo longitudinal magnetic resonance imaging measures of LC integrity, tau positron emission tomography imaging and cognition with autopsy data and transcriptomic information, we examined whether LC changes precede allocortical tau deposition and whether specific genetic features underlie LC's selective vulnerability to tau. We found that LC integrity changes preceded medial temporal lobe tau accumulation, and together these processes were associated with lower cognitive performance. Common gene expression profiles between LC-medial temporal lobe-limbic regions map to biological functions in protein transport regulation. These findings advance our understanding of the spatiotemporal patterns of initial tau spreading from the LC and LC's selective vulnerability to Alzheimer's disease pathology. LC integrity measures can be a promising indicator for identifying the time window when individuals are at risk of disease progression and underscore the importance of interventions mitigating initial tau spread.

Original language	English
Pages (from-to)	625-637
Number of pages	13
Journal	Nature aging
Volume	4
Issue number	5
DOIs	https://doi.org/10.1038/s43587-024-00626-y
Publication status	Published - May 2024

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@article{eed54ce583884714b876970619059c70,

title = "Spatiotemporal patterns of locus coeruleus integrity predict cortical tau and cognition",

abstract = "Autopsy studies indicated that the locus coeruleus (LC) accumulates hyperphosphorylated tau before allocortical regions in Alzheimer's disease. By combining in vivo longitudinal magnetic resonance imaging measures of LC integrity, tau positron emission tomography imaging and cognition with autopsy data and transcriptomic information, we examined whether LC changes precede allocortical tau deposition and whether specific genetic features underlie LC's selective vulnerability to tau. We found that LC integrity changes preceded medial temporal lobe tau accumulation, and together these processes were associated with lower cognitive performance. Common gene expression profiles between LC-medial temporal lobe-limbic regions map to biological functions in protein transport regulation. These findings advance our understanding of the spatiotemporal patterns of initial tau spreading from the LC and LC's selective vulnerability to Alzheimer's disease pathology. LC integrity measures can be a promising indicator for identifying the time window when individuals are at risk of disease progression and underscore the importance of interventions mitigating initial tau spread.",

author = "Elisenda Bueichek{\'u} and Ibai Diez and Chan-Mi Kim and Becker, {John Alex} and Koops, {Elouise A} and Kenneth Kwong and Papp, {Kathryn V} and Salat, {David H} and Bennett, {David A} and Rentz, {Dorene M} and Sperling, {Reisa A} and Johnson, {Keith A} and Jorge Sepulcre and Jacobs, {Heidi I L}",

year = "2024",

month = may,

doi = "10.1038/s43587-024-00626-y",

language = "English",

volume = "4",

pages = "625--637",

journal = "Nature aging",

issn = "2662-8465",

publisher = "Springer",

number = "5",

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TY - JOUR

T1 - Spatiotemporal patterns of locus coeruleus integrity predict cortical tau and cognition

AU - Bueichekú, Elisenda

AU - Diez, Ibai

AU - Kim, Chan-Mi

AU - Becker, John Alex

AU - Koops, Elouise A

AU - Kwong, Kenneth

AU - Papp, Kathryn V

AU - Salat, David H

AU - Bennett, David A

AU - Rentz, Dorene M

AU - Sperling, Reisa A

AU - Johnson, Keith A

AU - Sepulcre, Jorge

AU - Jacobs, Heidi I L

PY - 2024/5

Y1 - 2024/5

N2 - Autopsy studies indicated that the locus coeruleus (LC) accumulates hyperphosphorylated tau before allocortical regions in Alzheimer's disease. By combining in vivo longitudinal magnetic resonance imaging measures of LC integrity, tau positron emission tomography imaging and cognition with autopsy data and transcriptomic information, we examined whether LC changes precede allocortical tau deposition and whether specific genetic features underlie LC's selective vulnerability to tau. We found that LC integrity changes preceded medial temporal lobe tau accumulation, and together these processes were associated with lower cognitive performance. Common gene expression profiles between LC-medial temporal lobe-limbic regions map to biological functions in protein transport regulation. These findings advance our understanding of the spatiotemporal patterns of initial tau spreading from the LC and LC's selective vulnerability to Alzheimer's disease pathology. LC integrity measures can be a promising indicator for identifying the time window when individuals are at risk of disease progression and underscore the importance of interventions mitigating initial tau spread.

AB - Autopsy studies indicated that the locus coeruleus (LC) accumulates hyperphosphorylated tau before allocortical regions in Alzheimer's disease. By combining in vivo longitudinal magnetic resonance imaging measures of LC integrity, tau positron emission tomography imaging and cognition with autopsy data and transcriptomic information, we examined whether LC changes precede allocortical tau deposition and whether specific genetic features underlie LC's selective vulnerability to tau. We found that LC integrity changes preceded medial temporal lobe tau accumulation, and together these processes were associated with lower cognitive performance. Common gene expression profiles between LC-medial temporal lobe-limbic regions map to biological functions in protein transport regulation. These findings advance our understanding of the spatiotemporal patterns of initial tau spreading from the LC and LC's selective vulnerability to Alzheimer's disease pathology. LC integrity measures can be a promising indicator for identifying the time window when individuals are at risk of disease progression and underscore the importance of interventions mitigating initial tau spread.

U2 - 10.1038/s43587-024-00626-y

DO - 10.1038/s43587-024-00626-y

M3 - Comment/Letter to the editor

SN - 2662-8465

VL - 4

SP - 625

EP - 637

JO - Nature aging

JF - Nature aging

IS - 5

ER -

Spatiotemporal patterns of locus coeruleus integrity predict cortical tau and cognition

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