Diffuse Amyloid- β Plaques, Neurofibrillary Tangles, and the Impact of APOE in Elderly Persons' Brains Lacking Neuritic Amyloid Plaques

Erin L. Abner, Janna H. Neltner, Gregory A. Jicha, Ela Patel, Sonya L. Anderson, Donna M. Wilcock, Linda J. Van Eldik, Peter T. Nelson

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


Data from a large autopsy series were analyzed to address questions pertinent to primary age-related tauopathy (PART) and Alzheimer's disease (AD): what factors are associated with increased severity of neurofibrillary degeneration in brains that lack neuritic amyloid plaques?; is there an association between Apolipoprotein E (APOE) alleles and PART pathologic severity independent of amyloid-β (Aβ) deposits?; and, how do the stains used to detect plaques and tangles impact the experimental results? Neuropathologic data were evaluated from elderly research volunteers whose brain autopsies were performed at University of Kentucky Alzheimer's Disease Center (UK-ADC; N = 145 subjects). All of the included subjects' brains lacked neuritic amyloid plaques according to the CERAD diagnostic criteria and the average final MMSE score before death was 26.8±4.6 stdev. The study incorporated evaluation of tissue with both silver histochemical stains and immunohistochemical stains to compare results; the immunohistochemical stains (Aβ and phospho-tau) were scanned and quantified using digital pathologic methods. Immunohistochemical stains provided important advantages over histochemical stains due to sensitivity and detectability via digital methods. When AD-type pathology was in its presumed earliest phases, neocortical parenchymal Aβ deposits were associated with increased medial temporal lobe neurofibrillary tangles. The observation supports the NIA-AA consensus recommendation for neuropathologic diagnoses, because even these "diffuse" Aβ deposits signal that AD pathobiologic mechanisms are occurring. Further, the data were most compatible with the hypothesis that the APOE ϵ4 allele exerts its effect(s) via driving Aβ deposition, i.e., an "upstream" influence, rather than being associated directly with Aβ- independent PART pathology.

Original languageEnglish
Pages (from-to)1307-1324
Number of pages18
JournalJournal of Alzheimer's Disease
Issue number4
StatePublished - 2018

Bibliographical note

Publisher Copyright:
© 2018 - IOS Press and the authors. All rights reserved.


  • Aging
  • Genie
  • MAPT
  • SNAP
  • ScanScope
  • amyloid- β
  • hippocampus
  • neuropathology
  • oldest-old

ASJC Scopus subject areas

  • General Neuroscience
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health


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