Cited by 517Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

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Neocortical Neurofibrillary Tangles Correlate With Dementia Severity in Alzheimer's Disease

Bierer, L. M., Hof, P. R., Purohit, D. P., Carlin, L., Schmeidler, J., Davis, K. L., Perl, D. P.·1995·Archives of Neurology

DOI 10.1001/archneur.1995.00540250089017

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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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Blatt, G. J., & Kemper, T. L. (1999) · Cerebral cortex · doi:10.1007/978-1-4615-4885-0_9
Additional file 1 of Tau-proximity ligation assay reveals extensive previously undetected pathology prior to neurofibrillary tangles in preclinical Alzheimer’s disease
Bengoa‐Vergniory, N., Velentza‐Almpani, E., Silva, A. M., Scott, C., Vargas‐Caballero, M., Sastre, M., Wade‐Martins, R., & Alegre‐Abarrategui, J. (2021) · Figshare · doi:10.6084/m9.figshare.13663206
Additional file 1 of Visuospatial memory impairment as a potential neurocognitive marker to predict tau pathology in Alzheimer’s continuum
Seo, E. H., Lim, H. J., Yoon, H.-J., Choi, K. Y., Lee, J. J., Park, J. Y., Choi, S. H., Kim, H., Kim, B. C., & Lee, K. H. (2021) · Figshare · doi:10.6084/m9.figshare.16779366
Additional file 1 of Pathological tau drives ectopic nuclear speckle scaffold protein SRRM2 accumulation in neuron cytoplasm in Alzheimer’s disease
McMillan, P. J., Strovas, T. J., Baum, M., Mitchell, B. K., Eck, R. J., Hendricks, N. E., Wheeler, J. M., Latimer, C. S., Keene, C. D., & Kraemer, B. C. (2021) · Figshare · doi:10.6084/m9.figshare.14880602
Additional file 2 of Emergence of distinct and heterogeneous strains of amyloid beta with advanced Alzheimer’s disease pathology in Down syndrome
Maxwell, A. M., Yuan, P., Rivera, B. M., Schaaf, W., Mladinov, M., Prasher, V. P., Robinson, A., DeGrado, W. F., & Condello, C. (2021) · Figshare · doi:10.6084/m9.figshare.17696286
Additional file 1 of Dynamic network model reveals distinct tau spreading patterns in early- and late-onset Alzheimer disease
Lee, W. J., Cho, H., Baek, M. S., Kim, H.-K., Lee, J. H., Ryu, Y. H., Lyoo, C. H., & Seong, J.-K. (2022) · Figshare · doi:10.6084/m9.figshare.20887205
Additional file 1 of Emergence of distinct and heterogeneous strains of amyloid beta with advanced Alzheimer’s disease pathology in Down syndrome
Maxwell, A. M., Yuan, P., Rivera, B. M., Schaaf, W., Mladinov, M., Prasher, V. P., Robinson, A., DeGrado, W. F., & Condello, C. (2021) · Figshare · doi:10.6084/m9.figshare.17696280

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)
ORCID: Hof, P. R.
Purohit, D. P.
Schmeidler, J.
Davis, K. L.
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)
DOI: 10.1001/archneur.1995.00540250089017
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: 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, 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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Neocortical Neurofibrillary Tangles Correlate With Dementia Severity in Alzheimer's Disease

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