Cited by 416Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

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Locus coeruleus volume and cell population changes during Alzheimer's disease progression: A stereological study in human postmortem brains with potential implication for early‐stage biomarker discovery

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Theofilas, Panos, Ehrenberg, Alexander J., Dunlop, Sara, Di Lorenzo Alho, Ana T., Nguy, Austin, Leite, Renata Elaine Paraizo, Rodriguez, Roberta Diehl, Mejia, Maria B., Suemoto, Claudia K., Ferretti-Rebustini, Renata Eloah De Lucena, Polichiso, Livia, Nascimento, Camila F., Seeley, William W., Nitrini, Ricardo, Pasqualucci, Carlos Augusto, Jacob Filho, Wilson, Rueb, Udo, Neuhaus, John, Heinsen, Helmut, Grinberg, Lea T.·2017·Alzheimer's & Dementia

DOI 10.1016/j.jalz.2016.06.2362PMC PMC5298942

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Abstract

Introduction: Alzheimer's disease (AD) progression follows a specific spreading pattern, emphasizing the need to characterize those brain areas that degenerate first. The brainstem's locus coeruleus (LC) is the first area to develop neurofibrillary changes (neurofibrillary tangles [NFTs]). Methods: The methods include unbiased stereological analyses in human brainstems to estimate LC volume and neuronal population in controls and individuals across all AD stages. Results: As the Braak stage increases by 1 unit, the LC volume decreases by 8.4%. Neuronal loss started only midway through AD progression. Age‐related changes spare the LC. Discussion: The long gap between NFT accumulation and neuronal loss suggests that a second trigger may be necessary to induce neuronal death in AD. Imaging studies should determine whether LC volumetry can replicate the stage‐wise atrophy observed here and how these changes are specific to AD. LC volumetry may develop into a screening biomarker for selecting high‐yield candidates to undergo expensive and less accessible positron emission tomography scans and to monitor AD progression from presymptomatic stages.

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Authors: Theofilas, P., Ehrenberg, A. J., Dunlop, S., Di Lorenzo Alho, A. T., Nguy, A., Leite, R. E. P., Rodriguez, R. D., Mejia, M. B., Suemoto, C. K., Ferretti-Rebustini, R. E. D. L., Polichiso, L., Nascimento, C. F., Seeley, W. W., Nitrini, R., Pasqualucci, C. A., Jacob Filho, W., Rueb, U., Neuhaus, J., Heinsen, H., & Grinberg, L. T.
Affiliations: University of California, San Francisco (US)
Hospital Albert Einstein São Paulo Brazil
Department of Pathology, LIM-22 University of São Paulo Medical School São Paulo Brazil
Universidade de São Paulo (BR)
Division of Geriatrics University of Sao Paulo Medical School São Paulo Brazil
University of São Paulo, School of Nursing São Paulo Brazil
Department of Neurology University of Sao Paulo Medical School São Paulo Brazil
Goethe University Frankfurt (DE)
Corresponding author: Grinberg, Lea T.
ORCID: Theofilas, Panos
Ehrenberg, Alexander J.
Dunlop, Sara
Rodriguez, Roberta Diehl
Nascimento, Camila F.
Seeley, William W.
Pasqualucci, Carlos Augusto
Neuhaus, John
Heinsen, Helmut
Grinberg, Lea T.
Venue: Alzheimer's & Dementia
Publisher: Wiley
Published: 2016-08-08
Volume: 13
Issue: 3
Pages: 236-246
ISSN: 1552-5260 (ISSN-L)
1552-5279
DOI: 10.1016/j.jalz.2016.06.2362
PMC: PMC5298942
OpenAlex: W2513816257
Cited by: 416
References: 62
Citations by year: 2026: 38 · 2025: 60 · 2024: 53 · 2023: 55 · 2022: 56 · 2021: 55 · 2020: 34 · 2019: 24 · 2018: 22 · 2017: 19
FWCI: 17.42
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Alzheimer s & Dementia (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
eScholarship (California Digital Library) (submittedVersion)
Funders: National Institutes of Health (R01AG040311)
Sociedade Beneficente Israelita Brasileira Albert Einstein
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: Alzheimer's disease, locus coeruleus
MeSH terms: Adult, Aged, Aged, 80 and over, Alzheimer Disease, Autopsy, Female, Humans, Locus Coeruleus, Male, Middle Aged, Neurons, Stereotaxic Techniques, Biomarkers, Disease Progression

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Locus coeruleus volume and cell population changes during Alzheimer's disease progression: A stereological study in human postmortem brains with potential implication for early‐stage biomarker discovery

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