Progression of Alzheimer's Disease-Related Pathology and Cell Counts in a Patient with Idiopathic Normal Pressure Hydrocephalus

J Alzheimers Dis. 2018;61(4):1451-1462. doi: 10.3233/JAD-170446.

Abstract

We had an opportunity to assess the change observed in the brain regarding Alzheimer's disease (AD)-related alterations, cell count, and inflammation that took place during a period of 21 months in a subject with a definite diagnosis of AD and idiopathic Normal Pressure Hydrocephalus (iNPH). Four neuronal markers, i.e., synaptophysin, microtubule associated protein 2, non-phosphorylated neurofilament H (SMI32), and embryonic lethal abnormal visual system proteins 3/4 HuC/HuD (HuC/HuD); three microglial markers CD68, Human Leucocytic Antigen DR, ionized calcium-binding adaptor molecule 1, glial fibrillary acidic protein (GFAP); and AD-related markers, hyperphosphorylated τ (HPτ) and amyloid-β (Aβ, Aβ40, Aβ42) were assessed. Morphometrically assessed immunoreactivity of all neuronal and all microglial markers and Aβ42 decreased parallel with an increase in the HPτ in the frontal cortex. The expression of GFAP was stable with time. The first sample was obtained during the therapeutic shunting procedure for iNPH, and the second sample was obtained postmortem. Negligible reactive changes were observed surrounding the shunt channel. In conclusion, in the late stage of AD with time, a neuronal loss, increase in the HPτ, and decrease in Aβ42 and microglia was observed, whereas the expression of GFAP was rather stable. The observations described here suggest that when a brain biopsy has been obtained from an adult subject with iNPH, the assessment of postmortem brain is of major significance.

Keywords: Amyloid-β; astrocytes; hyperphosphorylated tau; idiopathic normal pressure hydrocephalus; immunohistochemistry; microglia; neurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / complications
  • Alzheimer Disease / pathology*
  • Amyloid beta-Peptides / metabolism*
  • Biomarkers / cerebrospinal fluid
  • Biomarkers / metabolism
  • Biopsy
  • Brain / metabolism*
  • Brain / pathology
  • Cell Count
  • Disease Progression
  • Female
  • Glial Fibrillary Acidic Protein / metabolism
  • Humans
  • Hydrocephalus, Normal Pressure / diagnosis*
  • Microglia / metabolism
  • tau Proteins / metabolism*

Substances

  • Amyloid beta-Peptides
  • Biomarkers
  • Glial Fibrillary Acidic Protein
  • tau Proteins