Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
Vulnerability of locus coeruleus connections to aging and Alzheimer's disease.
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Zufiria-Gerbolés Blanca, Vereb Daniel, Mijalkov Mite, Passaretti Massimiliano, Volpe Giovanni, Xu Zhilei, Hinault Thomas, Garcia-Ptacek Sara, Pereira Joana B, Alzheimer's Disease Neuroimaging Initiative
Аннотация
INTRODUCTION: The locus coeruleus (LC) is important in coordinating communication between brain regions through its widespread connections. However, the organization of its connections, and its changes with aging and Alzheimer's disease (AD), remains unclear.
METHODS: We mapped whole-brain white matter connections from the LC in two independent cohorts: one spanning the adult lifespan and another covering the AD continuum.
RESULTS: We identified a novel dorsal-ventral organization of LC connectivity that showed changes common to aging and AD or specific to AD, was linked to gene expression patterns, and was associated with cognitive performance and tau pathology in the entorhinal cortex. We also developed an imaging marker, LC gap, capturing LC connectivity deviations associated with slower tau accumulation in cognitively normal individuals at high risk for AD.
DISCUSSION: These findings provide new insights into LC connectivity in aging and AD, highlighting its potential role as a resilience marker against AD neurodegeneration.
METHODS: We mapped whole-brain white matter connections from the LC in two independent cohorts: one spanning the adult lifespan and another covering the AD continuum.
RESULTS: We identified a novel dorsal-ventral organization of LC connectivity that showed changes common to aging and AD or specific to AD, was linked to gene expression patterns, and was associated with cognitive performance and tau pathology in the entorhinal cortex. We also developed an imaging marker, LC gap, capturing LC connectivity deviations associated with slower tau accumulation in cognitively normal individuals at high risk for AD.
DISCUSSION: These findings provide new insights into LC connectivity in aging and AD, highlighting its potential role as a resilience marker against AD neurodegeneration.