Hippocampal sclerosis in the parkinsonism-dementia complex of Guam: quantitative examination of neurons, neurofibrillary tangles, and TDP-43 immunoreactivity in CA1

Neuropathology. 2015 Jun;35(3):224-35. doi: 10.1111/neup.12185. Epub 2015 Mar 18.

Abstract

The cornu ammonis 1 (CA1) area in the hippocampus of the parkinsonism-dementia complex (PDC) of Guam was examined quantitatively with special references to the number of neurons, intraneuronal (i) and extracellular (e) neurofibirillary tangles (NFTs), and TDP-43 (43-kDa trans-activation-responsive region DNA-binding protein)-immunopositive structures, in 24 Chamorro patients with PDC of Guam and seven control Chamorro Guamanians (both groups having no ischemic or anoxic complications). The results were that: (i) in the patients with mildly involved PDC, total numbers of neurons, iNFTs and eNFTs were almost the same as those of neurons of controls; (ii) in patients severely involved, total numbers of neurons, iNFTs and eNFTs decreased markedly; (iii) the decrease of the number of pyramidal neurons in CA1 with positive nuclear TDP-43 was intimately correlated with the decrease in total neuron numbers; (iv) whereas the numbers of neurons and TDP-43-immunopositive intracytoplasmic aggregation in the CA1 area were inversely correlated; and (v) depression of nuclear TDP-43 immuonostainability was not affected by the presence or absence of NFTs. In conclusion, hippocampal sclerosis exists in PDC; there is a possibility of elimination of eNFTs which appeared in the CA1 in patients with PDC and loss of the neurons correlates with disappearance of nuclear TDP-43, but not with appearance of intraneurocytoplasmic TDP-43 aggregation or iNFTs.

Keywords: CA1; Parkinsonism-dementia complex; TDP-43; hippocampal sclerosis; neurofibrillary tangle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • DNA-Binding Proteins / metabolism
  • Dementia / complications
  • Dementia / metabolism
  • Dementia / pathology*
  • Extracellular Space
  • Female
  • Guam
  • Hippocampus / metabolism
  • Hippocampus / pathology*
  • Humans
  • Male
  • Middle Aged
  • Neurofibrillary Tangles / metabolism
  • Neurofibrillary Tangles / pathology
  • Neurons / metabolism
  • Neurons / pathology
  • Parkinsonian Disorders / complications
  • Parkinsonian Disorders / metabolism
  • Parkinsonian Disorders / pathology*
  • Sclerosis

Substances

  • DNA-Binding Proteins
  • TARDBP protein, human