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.
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.
Nelson
Peter T
PT
Department of Pathology and Division of Neuropathology, Univerisity of Kentucky, Lexington, Kentucky 40536-0230, USA. pnels2@email.uky.edu
Abner
Erin L
EL
Schmitt
Frederick A
FA
Kryscio
Richard J
RJ
Jicha
Gregory A
GA
Santacruz
Karen
K
Smith
Charles D
CD
Patel
Ela
E
Markesbery
William R
WR
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000453:epidemiology / Q000473:pathology; D001921:Brain / Q000473:pathology*; D002540:Cerebral Cortex / Q000473:pathology; D003072:Cognition Disorders / Q000175:diagnosis* / Q000453:epidemiology / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D015994:Incidence; D007251:Influenza, Human / Q000453:epidemiology; D008297:Male; D016874:Neurofibrillary Tangles / Q000473:pathology*; D009474:Neurons / Q000473:pathology; D058225:Plaque, Amyloid / Q000473:pathology*; D013702:Temporal Lobe / Q000473:pathology