Cited by 396Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

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Locus coeruleus neurofibrillary degeneration in aging, mild cognitive impairment and early Alzheimer's disease

Grudzien, Aneta, Shaw, Pamela, Weintraub, Sandra, Bigio, Eileen, Mash, Deborah C., Mesulam, M. Marsel·2007·Neurobiology of Aging

DOI 10.1016/j.neurobiolaging.2006.02.007

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Abstract

Neurofibrillary degeneration in the nucleus basalis and a loss of its cortical cholinergic projections are prominent components of the neuropathology in Alzheimer's disease (AD). The AD brain is also associated with a degeneration of the noradrenergic projections arising from the nucleus locus coeruleus (LC), but the time course of this lesion is poorly understood. To determine whether the LC displays neurofibrillary abnormalities early in the course of events leading to AD, we examined tissue specimens from seven cognitively normal controls and five subjects at the stages of mild cognitively impairment (MCI) or early AD. Tyrosine hydroxylase immunochemistry was used as a marker of LC neurons while AT8 immunolabeling visualized abnormal tau associated with neurofibrillary tangles and their precursors. Thioflavine-S was used as a marker for fully developed tangles. We found that AT8-positive labeling and thioflavine-S positive tangles were present in both groups of specimens. However, the percentage of neurons containing each of these markers was significantly higher in the cognitively impaired group. The MMSE scores displayed a negative correlation with both markers of cytopathology. These results indicate that cytopathology in the LC is an early event in the age-MCI-AD continuum and that it may be listed among the numerous factors that mediate the emergence of the cognitive changes leading to dementia.

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Author Response: The gene expression landscape of the human locus coeruleus revealed by single-nucleus and spatially-resolved transcriptomics
Weber, L. M., Divecha, H. R., Tran, M. N., Kwon, S. H., Spangler, A., Montgomery, K. D., Tippani, M., Bharadwaj, R. A., Kleinman, J. E., Page, S. C., et al. (2023) · eLife · doi:10.7554/elife.84628.1.sa0
Reviewer #2 (Public Review): The gene expression landscape of the human locus coeruleus revealed by single-nucleus and spatially-resolved transcriptomics
(2023) · eLife · doi:10.7554/elife.84628.1.sa2
Reviewer #3 (Public Review): The gene expression landscape of the human locus coeruleus revealed by single-nucleus and spatially-resolved transcriptomics
(2023) · eLife · doi:10.7554/elife.84628.1.sa1
Reviewer #1 (Public Review): The gene expression landscape of the human locus coeruleus revealed by single-nucleus and spatially-resolved transcriptomics
(2023) · eLife · doi:10.7554/elife.84628.1.sa3
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Authors: Grudzien, A., Shaw, P., Weintraub, S., Bigio, E., Mash, D. C., & Mesulam, M. M.
Affiliations: Northwestern University (US)
University of Miami (US)
Corresponding author: Mesulam, M. Marsel
ORCID: Shaw, Pamela
Bigio, Eileen
Mash, Deborah C.
Mesulam, M. Marsel
Venue: Neurobiology of Aging
Publisher: Elsevier BV
Published: 2007-03
Volume: 28
Issue: 3
Pages: 327-335
ISSN: 0197-4580 (ISSN-L)
DOI: 10.1016/j.neurobiolaging.2006.02.007
OpenAlex: W2168697938
Cited by: 396
References: 45
Citations by year: 2026: 17 · 2025: 21 · 2024: 19 · 2023: 31 · 2022: 19 · 2021: 40 · 2020: 30 · 2019: 16 · 2018: 15 · 2017: 28 · 2016: 18 · 2015: 22 · 2014: 18 · 2013: 20 · 2012: 20
FWCI: 6.74
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neurobiology of Aging (publishedVersion)
PubMed (publishedVersion)
Funders: University of Miami
Northwestern University
National Institute on Aging (P30AG013854)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords: locus coeruleus, neurofibrillary degeneration, Alzheimer's disease, mild cognitive impairment, aging, tau protein, neurofibrillary tangles, noradrenergic projections, AT8, thioflavine S, tyrosine hydroxylase, cognitive decline, dementia
MeSH terms: Acetylcholinesterase, Aged, Aged, 80 and over, Aging, Alzheimer Disease, Cognition Disorders, Female, Humans, Immunohistochemistry, Locus Coeruleus, Male, Middle Aged, Postmortem Changes, Psychological Tests, Reference Values, Tyrosine 3-Monooxygenase, Neurofibrillary Tangles, tau Proteins, Statistics, Nonparametric

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Locus coeruleus neurofibrillary degeneration in aging, mild cognitive impairment and early Alzheimer's disease

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