Cited by 115Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Brains With Medial Temporal Lobe Neurofibrillary Tangles But No Neuritic Amyloid Plaques Are a Diagnostic Dilemma But May Have Pathogenetic Aspects Distinct From Alzheimer Disease

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Nelson, Peter T., Abner, Erin L., Schmitt, Frederick A., Kryscio, Richard J., Jicha, Gregory A., Santacruz, Karen, Smith, Charles D., Patel, Ela +1 more·2009·Journal of Neuropathology & Experimental Neurology

Abstract

Brains that have many neurofibrillary tangles (NFTs) in medial temporal lobe structures (Braak stage III or IV) but no cortical neuritic plaques (NPs) may be a diagnostic dilemma; they also raise questions about the amyloid cascade hypothesis of Alzheimer disease (AD) in which NFT development is thought to occur downstream of the development of amyloid plaques. To determine the clinical, demographic, and biological factors related to NFT+/NP- cases, we analyzed 26 NFT+/NP- patient brains identified from the University of Kentucky AD Center autopsy cohort (n=502); most of these patients were at least 85 years old and lacked profound antemortem cognitive impairment. A subset of the cases had NFTs in the medulla oblongata. Aberrant trans-activator regulatory DNA-binding protein 43 immunohistochemical staining was seen in 5 of the 26 cases with the clinical diagnoses of AD or mild cognitive impairment. We also queried cases in the National Alzheimer's Coordinating Center Registry (n=5,108) and found 219 NFT+/NP- cases. Those patients had a relatively high likelihood of belonging to a birth cohort with the highest incidence of influenza infection during the 1918 to 1919 pandemic. This observation may link the pathogenesis in NFT+/NP- cases to encephalitis during childhood. We conclude that NFT+/NP- cases comprise approximately 5% of aged individuals in multiple data sets; these cases are not necessarily within the spectrum of AD.

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  1. [31]Nelson PT Abner EL Schmitt FA Modeling the association between 43 different clinical and pathological variables and the severity of cognitive impairment in a large autopsy cohort of elderly persons Brain Pathol 2008 [Epub ahead of print] PMC2864342 19021630

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Authors
Nelson, P. T., Abner, E. L., Schmitt, F. A., Kryscio, R. J., Jicha, G. A., Santacruz, K., Smith, C. D., Patel, E., & Markesbery, W. R.
Affiliations
University of Kentucky (US)
Corresponding author
Nelson, Peter T.
Venue
Journal of Neuropathology & Experimental Neurology
Published
2009-07
Volume
68
Issue
7
Pages
774-784
ISSN
  • 0022-3069 (ISSN-L)
  • 1554-6578
OpenAlex
W2040124543
Cited by
115
References
74
Citations by year
2026: 4 · 2025: 13 · 2024: 7 · 2023: 6 · 2022: 7 · 2021: 10 · 2020: 6 · 2019: 2 · 2018: 3 · 2017: 9 · 2016: 5 · 2015: 6 · 2014: 5 · 2013: 11 · 2012: 6
FWCI
4.64
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuropathology & Experimental Neurology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (AG028 383, NS061933)
  • National Institute on Aging (P30AG028383, U01AG016976)
  • National Institute of Neurological Disorders and Stroke (R01NS061933, K08NS050110)
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
neurofibrillary tangles, neuritic plaques, Alzheimer's disease, medial temporal lobe, amyloid hypothesis, tau protein, medulla oblongata, pediatric encephalitis, mild cognitive impairment, differential diagnosis, Braak staging
MeSH terms
Aged, Aged, 80 and over, Alzheimer Disease, Brain, Cerebral Cortex, Cognition Disorders, Female, Humans, Immunohistochemistry, Influenza, Human, Male, Neurons, Temporal Lobe, Cohort Studies, Incidence, Neurofibrillary Tangles, Plaque, Amyloid

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