Document Detail

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.
MedLine Citation:
PMID:  19535994     Owner:  NLM     Status:  MEDLINE    
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.
Peter T Nelson; Erin L Abner; Frederick A Schmitt; Richard J Kryscio; Gregory A Jicha; Karen Santacruz; Charles D Smith; Ela Patel; William R Markesbery
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of neuropathology and experimental neurology     Volume:  68     ISSN:  0022-3069     ISO Abbreviation:  J. Neuropathol. Exp. Neurol.     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-06-30     Completed Date:  2009-08-10     Revised Date:  2014-09-20    
Medline Journal Info:
Nlm Unique ID:  2985192R     Medline TA:  J Neuropathol Exp Neurol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  774-84     Citation Subset:  IM    
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MeSH Terms
Aged, 80 and over
Alzheimer Disease / diagnosis*,  epidemiology,  pathology
Brain / pathology*
Cerebral Cortex / pathology
Cognition Disorders / diagnosis*,  epidemiology,  pathology
Cohort Studies
Influenza, Human / epidemiology
Neurofibrillary Tangles / pathology*
Neurons / pathology
Plaque, Amyloid / pathology*
Temporal Lobe / pathology
Grant Support
K08 NS050110/NS/NINDS NIH HHS; K08 NS050110/NS/NINDS NIH HHS; K08 NS050110-06/NS/NINDS NIH HHS; P30 AG028383/AG/NIA NIH HHS; P30 AG028383-01/AG/NIA NIH HHS; P30-AG028383/AG/NIA NIH HHS; R01 NS061933/NS/NINDS NIH HHS; R01 NS061933/NS/NINDS NIH HHS; R01 NS061933-02/NS/NINDS NIH HHS; U01 AG016976/AG/NIA NIH HHS

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