The importance of neuritic plaques and tangles to the development and evolution of AD

Tiraboschi, P.; Hansen, L. A.; Thal, L. J.; Corey-Bloom, J.

doi:10.1212/01.wnl.0000129697.01779.0a

Cited by 477Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

The importance of neuritic plaques and tangles to the development and evolution of AD

Tiraboschi, P., Hansen, L. A., Thal, L. J., Corey-Bloom, J.·2004·Neurology

DOI 10.1212/01.wnl.0000129697.01779.0a

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Abstract

OBJECTIVE: To determine the relation of neuritic plaques (NPs) and neurofibrillary tangles (NFTs) to the development and evolution of Alzheimer disease (AD). METHODS: An autopsy series of 102 patients with dementia and pathologically confirmed AD and 29 normal control subjects (NCs) was studied. AD cases were stratified according to their last Mini-Mental State Examination (MMSE) before death as mild, moderate, severe, or very severe. NPs and NFTs were enumerated in the midfrontal (MF), inferior parietal (IP), superior temporal (ST), hippocampal (Hip), or entorhinal cortices using thioflavin-S preparations. RESULTS: Most (87%) of the NCs had allocortical NFTs, whereas only a minority (37%) displayed neocortical NPs, and even fewer (19%) showed Hip NPs. In contrast, none of the NCs exhibited neocortical NFTs, except one case with a single ST tangle. However, neocortical NFTs were not detected in even 10% of the patients with AD and, in particular, were absent in nearly 50% of those with mild disease at death. Thus, their sensitivity as a marker of AD was lower than that of NPs, which, conversely, were found in all patients with AD. Comparing NCs and patients with mild AD, significant differences were found for numbers of NPs only. Across the AD groups, in contrast, although NP and NFT density increased with dementia severity, significant differences consistently emerged for NFTs alone. CONCLUSIONS: Deterioration in Alzheimer disease appears to be driven by neuritic plaques and neurofibrillary tangles at different stages of the disease. The significant increase in neuritic plaques, but not neurofibrillary tangles, in patients with even mild Alzheimer disease at death compared with normal control subjects suggests that only neuritic plaques are associated with the earliest symptoms of Alzheimer disease.

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The density of tau-positive NPs does correlate directly and statistically independently with some degree of cognitive impairment.
“On the other hand, the density of tau-positive NPs does correlate directly and statistically independently with some degree of cognitive impairment (105-107) (Fig. 2).”
From Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature (2012) · cites this paper as [106]
Subsequent studies have established that the densities of NPs correlate with antemortem cognitive impairment better than the densities of diffuse AβPs.
“Subsequent studies have established that the densities of NPs correlate with antemortem cognitive impairment better than the densities of diffuse AβPs (45, 98, 106, 154, 189, 261).”
From Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature (2012) · cites this paper as [106]

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Authors: Tiraboschi, P., Hansen, L. A., Thal, L. J., & Corey-Bloom, J.
Affiliations: University of California San Diego (US)
From the Dipartimento di Scienze Neurologiche (Dr. Tiraboschi), Ospedale Niguarda Ca’ Granda, Milan, Italy; Department of Neurosciences (Drs. Hansen, Thal, and Corey-Bloom), University of California, San Diego, La Jolla, CA; and Neurology Service (Drs. Thal and Corey-Bloom), VA San Diego Healthcare System, San Diego, CA.
ORCID: Tiraboschi, P.
Hansen, L. A.
Venue: Neurology
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2004-06-08
Volume: 62
Issue: 11
Pages: 1984-1989
ISSN: 0028-3878 (ISSN-L)
1526-632X
DOI: 10.1212/01.wnl.0000129697.01779.0a
OpenAlex: W2081126811
Cited by: 477
References: 44
Citations by year: 2026: 5 · 2025: 12 · 2024: 15 · 2023: 15 · 2022: 17 · 2021: 17 · 2020: 27 · 2019: 35 · 2018: 26 · 2017: 20 · 2016: 23 · 2015: 37 · 2014: 48 · 2013: 26 · 2012: 37
FWCI: 6.18
Type: journal article
Language: en
Open access: closed
Locations: Neurology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute on Aging (AG05131, P50AG005131)
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, neuritic plaques, neurofibrillary tangles, disease progression, dementia severity, thioflavin S staining, neuropathology
MeSH terms: Adult, Aged, Aged, 80 and over, Alzheimer Disease, Brain, California, Female, Follow-Up Studies, Humans, Male, Middle Aged, Neuropsychological Tests, Cohort Studies, Neurofibrillary Tangles, Disease Progression, Plaque, Amyloid

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The importance of neuritic plaques and tangles to the development and evolution of AD

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