Neocortical Neurofibrillary Tangles Correlate With Dementia Severity in Alzheimer's Disease
Abstract
OBJECTIVE: To determine the relationships between dementia severity and the extent of histopathologic lesions in a variety of brain regions. Neocortical and hippocampal ratings for neurofibrillary tangles (NFTs) and senile plaques (SPs) were compared in 70 cases of clinically and neuropathologically confirmed Alzheimer's disease. DESIGN: Neuropathologic case series. Dementia severity was assessed by postmortem chart review with use of the extended Clinical Dementia Rating Scale (CDR). Linear association between CDR scores and NFT and SP scores were assessed by partial correlation, controlling for age at death. SETTING: Studies were conducted at the Alzheimer's Disease Research Center of the Mount Sinai Medical Center, New York, NY. MAIN OUTCOME MEASURE: Association between CDR scores and neuropathologic changes assessed with the Consortium to Establish a Registry for Alzheimer's Disease semiquantitative scale. RESULTS: Among these lesion scores, only NFTs showed a significant association with CDR score, and only for neocortical regions. In particular, NFT densities in the superior temporal cortex were most strongly correlated with dementia severity, followed by those in the inferior parietal and midfrontal cortex. No such correlations were apparent for the amygdala, hippocampus, or entorhinal cortex. Medial temporal lobe structures displayed high NFT scores, even in cases of mild dementia. Senile plaques did not correlate significantly with CDR score in any region. CONCLUSIONS: These data support the notion that neocortical neuronal degeneration, as indicated by NFT formation, is a critical determinant of the clinical progression of Alzheimer's disease and suggest that medial temporal lobe structures may represent the initial site of NFT formation. While SP density correlates with age at death, there is no correlation between SP counts and dementia severity. These results further suggest that the clinical presentation of dementia may be closely related to neurodegeneration in neocortical regions within the temporal lobe.
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Studies have shown that the number and location of neurofibrillary tangles correlates with neuronal loss, disease severity and clinical course.
“Studies have shown that their number and location correlates with neuronal loss, disease severity and clinical course [65, 66].”
From The neuropathological diagnosis of Alzheimer's disease (2019) · cites this paper as [65]
Neurofibrillary tangles and quantitative neuronal loss, but not amyloid plaques, correlate with disease severity and dementia duration.
“Neurofibrillary tangles and quantitative neuronal loss, but not amyloid plaques, have been found to correlate with disease severity and dementia duration [21–23].”
From Clinical trials of new drugs for Alzheimer disease (2020) · cites this paper as [23]
Tau pathology correlates with cognitive decline in AD.
“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 Bierer et al., 1995
NFTs and quantitative neuronal loss may be more closely correlated with disease severity and dementia progression than the amyloid plaque burden.
“NFTs and quantitative neuronal loss may be more closely correlated with disease severity and dementia progression than the amyloid plaque burden [20–22].”
From Clinical trials of new drugs for Alzheimer disease: a 2020–2023 update (2023) · cites this paper as [22]
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- Authors
- Bierer, L. M., Hof, P. R., Purohit, D. P., Carlin, L., Schmeidler, J., Davis, K. L., & Perl, D. P.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Venue
- Archives of Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 1995-01-01
- Volume
- 52
- Issue
- 1
- Pages
- 81-88
- ISSN
- 0003-9942 (ISSN-L)
- OpenAlex
- W2084957666
- Cited by
- 514
- References
- 40
- Citations by year
- 2026: 7 · 2025: 16 · 2024: 15 · 2023: 22 · 2022: 24 · 2021: 27 · 2020: 21 · 2019: 25 · 2018: 23 · 2017: 17 · 2016: 20 · 2015: 17 · 2014: 18 · 2013: 14 · 2012: 14
- FWCI
- 10.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG-02219, AG 05138, P50AG005138, AG-00408, P01AG002219)
- Topics
- Health Sciences › Medicine › Physiology › 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, neurofibrillary tangles, dementia severity, amyloid plaques, neocortex, hippocampus, medial temporal lobe, superior temporal cortex, inferior parietal cortex, Clinical Dementia Rating, neuropathology, neurodegeneration, clinical progression
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Dementia, Female, Humans, Male, Middle Aged, Neurofibrillary Tangles
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