Progressive white matter pathology in the spinal cord of transgenic mice expressing mutant (P301L) human tau

Wen Lang Lin, Cindy Zehr, Jada Lewis, Michael Hutton, Shu Hui Yen, Dennis W Dickson

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Transgenic mice expressing mutant (P301L) tau develop paresis, neurofibrillary tangles and neuronal loss in spinal motor neurons beginning at 4 to 6 months of age. Astrocytes and oligodendrocytes acquire filamentous tau inclusions at later ages. Here we report pathology in the spinal white matter of these animals. Progressive white matter pathology, detected as early as 2 months of age, was most marked in lateral and anterior columns, with sparing of posterior columns until late in the disease. Early changes in Luxol fast blue/periodic acid Schiff (LFB/PAS) and toluidine blue stained sections were vacuolation of myelin followed by accumulation of myelin figures within previous axonal tubes and finally influx of PAS-positive macrophages. Myelin debris and vacuoles were found in macrophages. At the ultrastructural level, myelinated axons showed extensive vacuolation of myelin sheaths formed by splitting of myelin lamellae at the intra-period line, while axons were atrophic and contained densely packed neurofilaments. Other axons were lost completely, resulting in collapse and phagocytosis of myelin sheaths. Also present were spheroids derived from swollen axons with thin myelin sheaths containing neurofilaments, tau filaments and degenerating organelles. Many oligodendrocytes had membrane-bound cytoplasmic bodies composed of tightly stacked lamellae capped by dense material. The vacuolar myelopathy in this model to some extent resembles that reported in acquired immune deficiency syndrome and vitamin B12 deficiency. The progressive axonal pathology is most consistent with a dying-back process caused by abnormal accumulation of tau in upstream neurons, while vacuolar myelinopathy may be a secondary manifestation of neuroinflammation.

Original languageEnglish (US)
Pages (from-to)397-410
Number of pages14
JournalJournal of Neurocytology
Volume34
Issue number6
DOIs
StatePublished - Dec 2006

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Myelin Sheath
Transgenic Mice
Spinal Cord
Pathology
Axons
Intermediate Filaments
Oligodendroglia
Macrophages
Vitamin B 12 Deficiency
Tolonium Chloride
Neurofibrillary Tangles
Periodic Acid
Spinal Cord Diseases
Motor Neurons
Paresis
Vacuoles
White Matter
Phagocytosis
Astrocytes
Organelles

ASJC Scopus subject areas

  • Neuroscience(all)
  • Anatomy
  • Cell Biology
  • Histology

Cite this

Progressive white matter pathology in the spinal cord of transgenic mice expressing mutant (P301L) human tau. / Lin, Wen Lang; Zehr, Cindy; Lewis, Jada; Hutton, Michael; Yen, Shu Hui; Dickson, Dennis W.

In: Journal of Neurocytology, Vol. 34, No. 6, 12.2006, p. 397-410.

Research output: Contribution to journalArticle

Lin, Wen Lang ; Zehr, Cindy ; Lewis, Jada ; Hutton, Michael ; Yen, Shu Hui ; Dickson, Dennis W. / Progressive white matter pathology in the spinal cord of transgenic mice expressing mutant (P301L) human tau. In: Journal of Neurocytology. 2006 ; Vol. 34, No. 6. pp. 397-410.
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