The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
Locus coeruleus neurofibrillary degeneration in aging, mild cognitive impairment and early Alzheimer's disease
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Subsequent studies identified the locus coeruleus as the first site of pathology in AD subjects, with NFTs preceding cortical tau or Aβ deposits [41–43].”
From Systems-based proteomics to resolve the biology of Alzheimer’s disease beyond amyloid and tau (2021) · cites this paper as [42]
In the citing paper
“As AD progresses, the NFTs become numerous in locus coeruleus which may suggest the same pathogenetic process is becoming more severe (301).”
From Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature (2012) · cites this paper as [301]
Citations
Cites
Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975) · Journal of Psychiatric Research · doi:10.1016/0022-3956(75)90026-6 · Cited by 88,282
Mild Cognitive Impairment: Clinical Characterization and Outcome
Petersen, R. C., Smith, G. E., Waring, S. C., Ivnik, R. J., Tangalos, E. G., & Kokmen, E. (1999) · Archives of Neurology · doi:10.1001/archneur.56.3.303 · Cited by 8,980
Mild cognitive impairment as a diagnostic entity
Petersen, R. C. (2004) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2004.01388.x · Cited by 7,864
Mirra, S. S., Heyman, A., McKeel, D., Sumi, S. M., Crain, B. J., Brownlee, L. M., Vogel, F. S., Hughes, J. P., Belle, G. V., Berg, L., et al. (1991) · Neurology · doi:10.1212/wnl.41.4.479 · Cited by 4,961
Moms, J. C., Heyman, A., Mohs, R. C., Hughes, J. P., van Belle, G., Fillenbaum, G., Mellits, E. D., & Clark, C. (1989) · Neurology · doi:10.1212/wnl.39.9.1159 · Cited by 4,130
Psychopharmacology: The Fourth Generation of Progress
Bloom, F. E., & Kupfer, D. J. (1995) · Medical Entomology and Zoology · Cited by 2,985
Population-Based Norms for the Mini-Mental State Examination by Age and Educational Level
Crum, R. M. (1993) · JAMA · doi:10.1001/jama.1993.03500180078038 · Cited by 2,958
Consortium to Establish a Registry for Alzheimer's Disease (CERAD)
Fillenbaum, G., & Heyman, A. (2002) · doi:10.1002/0470846410.ch42(iii · Cited by 2,859
A Compendium of Neuropsychological Tests
Selnes, O. A. (1991) · Neurology · doi:10.1212/wnl.41.11.1856-a · Cited by 2,278
Psychopharmacology: The Fourth Generation of Progress
Green, A. I. (1996) · Psychiatric Services · doi:10.1176/ps.47.3.312 · Cited by 1,147
Zarow, C., Lyness, S. A., Mortimer, J. A., & Chui, H. C. (2003) · Archives of Neurology · doi:10.1001/archneur.60.3.337 · Cited by 1,003
Cytoarchitecture of the Human Brain Stem.
Boyd, J. D. (1955) · Archives of Ophthalmology · doi:10.1001/archopht.1955.00930010774037 · Cited by 897
Braak, F., Braak, H., & Mandelkow, E. (1994) · Acta Neuropathologica · doi:10.1007/bf00293315 · Cited by 769
Evolution of the neuropathology of Alzheimer's disease
Braak, H., & Braak, E. (1996) · Acta Neurologica Scandinavica · doi:10.1111/j.1600-0404.1996.tb05866.x · Cited by 710
Multilingual Aphasia Examination
Patterson, J. P. (2010) · Springer eBooks · doi:10.1007/978-0-387-79948-3_900 · Cited by 686
Ivnik, R. J., Malec, J. F., Smith, G. E., Tangalos, E. G., & Petersen, R. C. (1996) · The Clinical Neuropsychologist · doi:10.1080/13854049608406689 · Cited by 547
Mesulam, M. M., Hoesen, G. W. V., Pandya, D. Ν., & Geschwind, N. (1977) · Brain Research · doi:10.1016/0006-8993(77)90066-x · Cited by 536
Self-citationMesulam, M. M., & Geula, C. (1988) · The Journal of Comparative Neurology · doi:10.1002/cne.902750205 · Cited by 520
Self-citationChan‐Palay, V., & Asan, E. (1989) · The Journal of Comparative Neurology · doi:10.1002/cne.902870308 · Cited by 493
Advances in the early detection of Alzheimer's disease
Nestor, P. J., Scheltens, P., & Hodges, J. R. (2004) · Nature Medicine · doi:10.1038/nrn1433 · Cited by 480
Neuroplasticity Failure in Alzheimer's Disease
Mesulam, M.-M. (1999) · Neuron · doi:10.1016/s0896-6273(00)81109-5 · Cited by 449
Self-citationPopulation-based norms for the Mini-Mental State Examination by age and educational level
Crum, R. M. (1993) · JAMA · doi:10.1001/jama.269.18.2386 · Cited by 449
Mayo's older americans normative studies: WAIS-R norms for ages 56 to 97
Ivnik, R. J., Malec, J. F., Smith, G. E., Tangalos, E. G., Petersen, R. C., Kokmen, E., & Kurland, L. T. (1992) · The Clinical Neuropsychologist · doi:10.1080/13854049208401877 · Cited by 446
The neuropathology of aminergic nuclei in Alzheimer's disease
Zweig, R. M., Ross, C. A., Hedreen, J. C., Steele, C., Cardillo, J. E., Whitehouse, P. J., Folstein, M. F., & Price, D. L. (1988) · Annals of Neurology · doi:10.1002/ana.410240210 · Cited by 446
Cholinergic nucleus basalis tauopathy emerges early in the aging‐MCI‐AD continuum
Mesulam, M. M., Shaw, P. L., Mash, D. C., & Weıntraub, S. (2004) · Annals of Neurology · doi:10.1002/ana.20100 · Cited by 365
Self-citationButyrylcholinesterase in the life cycle of amyloid plaques
Guillozet-Bongaarts, A. L., Mesulam, M. M., Smiley, J. F., & Mash, D. C. (1997) · Annals of Neurology · doi:10.1002/ana.410420613 · Cited by 313
Self-citationIshii, T. (1966) · Acta Neuropathologica · doi:10.1007/bf00686763 · Cited by 303
Cytoarchitecture of the Human Brain Stem
Bandler, R. J. (1983) · Pathology · doi:10.1016/s0031-3025(16)37288-9 · Cited by 300
Neurochemical Correlates of Major Depression in Primary Dementia
Zubenko, G. S., Moossy, J. J., & Kopp, U. (1990) · Archives of Neurology · doi:10.1001/archneur.1990.00530020117023 · Cited by 232
Phasic Activation of Monkey Locus Ceruleus Neurons by Simple Decisions in a Forced-Choice Task
Clayton, E. C., Rajkowski, J., Cohen, J. D., & Aston‐Jones, G. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.2446-04.2004 · Cited by 226
NEURONAL DEGENERATION IN LOCUS CERULEUS AND CORTICAL CORRELATES OF ALZHEIMER DISEASE
Bondareff, W., Mountjoy, C. Q., Roth, M., Rossor, M. N., Iversen, L. L., Reynolds, G. P., & Hauser, D. L. (1987) · Alzheimer Disease & Associated Disorders · doi:10.1097/00002093-198701040-00005 · Cited by 166 · cited 3×
“[3] Bondareff W, Mountjoy CQ, Rossor RM, Iversen LL, Reynolds GP, Hauser DL.”
BackgroundResultDevilbiss, D. M., & Waterhouse, B. D. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.1573-04.2004 · Cited by 162
The pathology of the human locus ceruleus.
Mann, D. M. A., Yates, P. O., & Hawkes, J. (1983) · PubMed · Cited by 161
Mayo's older americans normative studies: WMS-R norms for ages 56 to 94
Ivnik, R. J., Malec, J. F., Smith, G. E., Tangalos, E. G., Petersen, R. C., Kokmen, E., & Kurland, L. T. (1992) · The Clinical Neuropsychologist · doi:10.1080/13854049208401879 · Cited by 147
Effects of Alzheimer's disease severity on cerebrospinal fluid norepinephrine concentration
Elrod, R., Peskind, E. R., DiGiacomo, L., Brodkin, K. I., Veith, R. C., & Raskind, M. A. (1997) · American Journal of Psychiatry · doi:10.1176/ajp.154.1.25 · Cited by 140
Unbiased Estimation of Neuronal Numbers in the Human Nucleus Coeruleus during Aging
Ohm, T. G., Busch, C., & Bohl, J. R. E. (1997) · Neurobiology of Aging · doi:10.1016/s0197-4580(97)00034-1 · Cited by 126
Raskind, M. A., Peskind, E. R., Holmes, C. S., & Goldstein, D. S. (1999) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00008-6 · Cited by 106
Age and Histopathologic Heterogeneity in Alzheimer's Disease
Bondareff, W. (1987) · Archives of General Psychiatry · doi:10.1001/archpsyc.1987.01800170026005 · Cited by 94
The projection of the locus coeruleus upon the neocortex in the macaque monkey
Gatter, K. C., & Powell, T. P. S. (1977) · Neuroscience · doi:10.1016/0306-4522(77)90009-4 · Cited by 78
Neuronal activity and early neurofibrillary tangles in Alzheimer's disease
Hatanpaa, K. J., Brady, D. R., Stoll, J., Rapoport, S. I., & Chandrasekaran, K. (1996) · Annals of Neurology · doi:10.1002/ana.410400310 · Cited by 67
Tyrosine hydroxylase immunohistochemistry in human brain
Pearson, J. M., Goldstein, M., & Brandeis, L. (1979) · Brain Research · doi:10.1016/0006-8993(79)90565-1 · Cited by 66
Tohgi, H., Ueno, M., Abe, T., Takahashi, S., & Nozaki, Y. (1992) · Journal of Neural Transmission - Parkinsons Disease and Dementia Section · doi:10.1007/bf02257623 · Cited by 61
Monteiro, I. M., Boksay, I., Auer, S., Torossian, C. L., Sinaiko, E. A., & Reisberg, . (1998) · Journal of Geriatric Psychiatry and Neurology · doi:10.1177/089198879801100105 · Cited by 45
Dm, M., Yates, P. O., & Marcyniuk, B. (1985) · PubMed · Cited by 41
Laboratory examinations correlated with severity of dementia.
Oishi, M., Mochizuki, Y., Yoshihashi, H., Takasu, T., & Nakano, E. (1996) · PubMed · Cited by 32
Research works printed but not linked: 1
- Knight, 1970, Histochemical demonstration of the catecholamines and acetylcholine esterase in the same cell bodies in the locus ceruleus (rat hind brain), Proc R Microsc Soc, 6, 26
Cited by
Sorted by citations
Stages of the Pathologic Process in Alzheimer Disease: Age Categories From 1 to 100 Years
Braak, H., Thal, D. R., Ghebremedhin, E., & Del Tredici, K. (2011) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e318232a379 · Cited by 2,194
Nelson, P. T., Alafuzoff, I., Bigio, E. H., Bouras, C., Braak, H., Cairns, N. J., Castellani, R. J., Crain, B. J., Davies, P., Tredici, K. D., et al. (2012) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e31825018f7 · Cited by 2,050
“As AD progresses, the NFTs become numerous in locus coeruleus which may suggest the same pathogenetic process is becoming more severe (301).”
BackgroundSelf-citationPrimary age-related tauopathy (PART): a common pathology associated with human aging
Crary, J. F., Trojanowski, J. Q., Schneider, J. A., Abisambra, J. F., Abner, E. L., Alafuzoff, I., Arnold, S. E., Attems, J., Beach, T. G., Bigio, E. H., et al. (2014) · Acta Neuropathologica · doi:10.1007/s00401-014-1349-0 · Cited by 1,467
Self-citationClassification and basic pathology of Alzheimer disease
Duyckaerts, C., Delatour, B., & Potier, M.-C. (2009) · Acta Neuropathologica · doi:10.1007/s00401-009-0532-1 · Cited by 1,031
The neuropathology of probable Alzheimer disease and mild cognitive impairment
Schneider, J. A., Arvanitakis, Z., Leurgans, S. E., & Bennett, D. A. (2009) · Annals of Neurology · doi:10.1002/ana.21706 · Cited by 935
Metadata
- 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
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2007-03
- Volume
- 28
- Issue
- 3
- Pages
- 327-335
- ISSN
- 0197-4580 (ISSN-L)
- 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
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
