The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
Tangle and neuron numbers, but not amyloid load, predict cognitive status in Alzheimer’s disease
Open accessAbstract
OBJECTIVE: To examine the relationship between stereologic estimates of AD-related pathology and severity of cognitive deficits in brain aging. BACKGROUND: Previous studies reported substantial contributions of neurofibrillary tangles (NFT), amyloid deposits, and neuronal loss to the development of dementia. However, the prediction of cognitive status based on nonstereologic quantification of these measures has led to conflicting results. Such studies have measured densities, rather than absolute numbers, and most do not take into account the potential interaction between the above pathologic hallmarks in a global multivariate analysis. METHODS: Clinicopathologic study in 22 elderly cases. Cognitive status assessed prospectively using the Mini-Mental State Examination (MMSE); stereologic assessment of NFT, unaffected neurons, and total amyloid volume in the CA1 field of the hippocampus, entorhinal cortex, and area 9. Statistical analysis was performed using both univariate and multivariate linear regression models. RESULTS: High total NFT counts but not amyloid volume were strongly associated with a lower number of unaffected neurons in all areas studied. A high proportion of variability in MMSE scores was explained by NFT and neuronal counts in the CA1 field (83% and 85.4%), entorhinal cortex (87.8% and 83.7%), and area 9 (87% and 79%); amyloid volume in the entorhinal cortex, but not in the CA1 field and area 9, accounted for 58.5% of MMSE variability. Multivariate analyses showed that total NFT counts in the entorhinal cortex and area 9 as well as neuron numbers in the CA1 field were the best predictors of MMSE score. CONCLUSIONS: These new stereologic data indicate that neuronal pathology in hippocampal formation and frontal cortex closely reflects the progression of cognitive deficits in brain aging and AD. They also demonstrate that amyloid volume has no additional predictive value, in terms of clinicopathologic correlations, beyond its interaction with NFT.
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In the citing paper
“Even though extracellular amyloid plaque deposits had long been considered the principal players in the development and progression of AD, this association has been challenged by a poor correlation with the disease status [11]”
From Neuron Loss in Alzheimer’s Disease: Translation in Transgenic Mouse Models (2020) · cites this paper as [11]
In the citing paper
“In particular, loss of neurons in the CA1 region of the hippocampus [22,23] and in the entorhinal cortex seems to correlate with the severity of memory deficits [11].”
From Neuron Loss in Alzheimer’s Disease: Translation in Transgenic Mouse Models (2020) · cites this paper as [11]
In the citing paper
“Cognitive impairment correlates with the number of neurofibrillary tangles137, which selectively affect highly connected pyramidal cells in association cortex but not in primary sensory cortex6,138,139.”
From Stress weakens prefrontal networks: molecular insults to higher cognition (2015) · cites this paper as [137]
In the citing paper
“Occurrence of Tau deposits correlates with the loss of cognitive functions in AD, suggesting a connection between Tau and synaptic transmission20.”
From Multivalent cross-linking of actin filaments and microtubules through the microtubule-associated protein Tau (2017) · cites this paper as [20]
In the citing paper
“The progression of tau pathology has been correlated with memory dysfunction and cognitive impairments in AD (DeVos et al., 2018; Giannakopoulos et al., 2003).”
From Cholesterol 25-hydroxylase mediates neuroinflammation and neurodegeneration in a mouse model of tauopathy (2024) · cites this paper as Giannakopoulos et al., 2003
In the citing paper
“pathological tau aggregates, in the absence of amyloid plaques, can induce neurotoxicity, chronic brain inflammation, and subsequent cognitive impairment in many primary human tauopathies, including Pick's disease (PiD), progressive supranuclear palsy (PSP), and corticobasal degeneration. 4 , 5 , 6”
From Senescence, brain inflammation, and oligomeric tau drive cognitive decline in Alzheimer's disease: Evidence from clinical and preclinical studies (2024) · cites this paper as [4]
In the citing paper
“In AD patients, the clinical severity of dementia strongly correlates with the load of pathological tau aggregates. 3 , 4”
From Senescence, brain inflammation, and oligomeric tau drive cognitive decline in Alzheimer's disease: Evidence from clinical and preclinical studies (2024) · cites this paper as [4]
In the citing paper
“Unlike Aβ, the stage of tau pathology correlates well with progression of cognitive impairment”
From Alzheimer Disease: An Update on Pathobiology and Treatment Strategies (2019) · cites this paper as Giannakopoulos et al., 2003
In the citing paper
“Although apoE interacts with amyloid, it should be noted that plaque load does not correlate well with cognitive impairments, highlighted most obviously by people with substantial plaque burdens and normal cognition [67].”
From Apolipoprotein E4, inhibitory network dysfunction, and Alzheimer’s disease (2019) · cites this paper as [67]
In the citing paper
“correlation of Tau pathology with cognitive decline in AD (Arriagada et al., 1992; Bierer et al., 1995; Giannakopoulos et al., 2003; Gómez-Isla et al., 1997)”
From Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease (2020) · cites this paper as Giannakopoulos et al., 2003
In the citing paper
“the best pathological correlate for clinical symptoms to date is the extent of NFT formation (Arriagada et al., 1992; Brier et al., 2016; Giannakopoulos et al., 2003)”
From Selective Neuronal Vulnerability in Alzheimer’s Disease: A Network-Based Analysis (2020) · cites this paper as Giannakopoulos et al., 2003
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Self-citationCorrelation Between Elevated Levels of Amyloid β-Peptide in the Brain and Cognitive Decline
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Long, J. M., & Holtzman, D. M. (2019) · Cell · doi:10.1016/j.cell.2019.09.001 · Cited by 3,204
Neuropathological alterations in Alzheimer disease
Serrano-Pozo, A., Frosch, M. P., Masliah, E., & Hyman, B. T. (2011) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006189 · Cited by 3,345
Alzheimer Mechanisms and Therapeutic Strategies
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Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases
Loh, J. S., Mak, W. Q., Tan, L. K. S., Ng, C. X., Chan, H. H., Yeow, S. H., Foo, J. B., Ong, Y. S., How, C. W., & Khaw, K. Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01743-1 · Cited by 1,193
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Metadata
- Authors
- Giannakopoulos, P., Herrmann, F. R., Bussière, T., Bouras, C., Kövari, E., Perl, D. P., Morrison, J. H., Gold, G., & Hof, P. R.
- Affiliations
- University of Geneva (CH)
- From the Departments of Psychiatry (Drs. Giannakopoulos, Bouras, and Kövari) and Geriatrics (Drs. Herrmann and Gold), HUG Belle-Idée, University of Geneva School of Medicine; Department of Psychogeriatrics (Dr. Giannakopoulos), University of Lausanne School of Medicine, Switzerland; Kastor Neurobiology of Aging Laboratories and Fishberg Research Center for Neurobiology (Drs. Bussière, Bouras, Perl, Morrison, and Hof) and Departments of Geriatrics and Adult Development (Drs. Morrison and Hof),...
- Venue
- Neurology
- Published
- 2003-05-13
- Volume
- 60
- Issue
- 9
- Pages
- 1495-1500
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W2066792703
- Cited by
- 1,118
- References
- 49
- Citations by year
- 2026: 27 · 2025: 52 · 2024: 57 · 2023: 60 · 2022: 64 · 2021: 72 · 2020: 87 · 2019: 64 · 2018: 65 · 2017: 54 · 2016: 62 · 2015: 56 · 2014: 56 · 2013: 45 · 2012: 51
- FWCI
- 11.66
- Type
- journal article
- Language
- en
- Open access
- Licence
- cc-by
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion)
- Funders
- National Institute on Aging (AG-02219, AG 05138, P50AG005138, P01AG002219)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- Alzheimer's disease, neurofibrillary tangles, amyloid plaques, neuronal loss, cognitive decline, stereology, hippocampal CA1, entorhinal cortex, frontal cortex, amygdala, Mini-Mental State Examination, dementia prediction, clinicopathological correlation
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Cognition, Female, Frontal Lobe, Hippocampus, Humans, Male, Middle Aged, Neuropsychological Tests, Peptide Fragments, Severity of Illness Index, Single-Blind Method, Amyloid beta-Peptides, Neurofibrillary Tangles, tau Proteins, Entorhinal Cortex
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