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Mitochondrial degeneration in dystrophic neurites of senile plaques may lead to extracellular deposition of fine filaments

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Abstract

Recent data show that amyloid precursor protein accumulates inside axons after disruption of fast axonal transport, but how this leads to mature plaques with extracellular amyloid remains unclear. To investigate this issue, primitive plaques in prefrontal cortex of aged rhesus monkeys were reconstructed using serial section electron microscopy. The swollen profiles of dystrophic neurites were found to be diverticula from the main axis of otherwise normal neurites. Microtubules extended from the main neurite axis into the diverticulum to form circular loops or coils, providing a transport pathway for trapping organelles. The quantity and morphology of organelles contained within diverticula suggested a progression of degeneration. Primitive diverticula contained microtubules and normal mitochondria, while larger, presumably older, diverticula contained large numbers of degenerating mitochondria. In advanced stages of degeneration, apparent autophagosomes derived from mitochondria exhibited a loose lamellar to filamentous internal structure. Similar filamentous material and remnants of mitochondria were visible in the extracellular spaces of plaques. This progression of degeneration suggests that extracellular filaments originate inside degenerating mitochondria of neuritic diverticula, which may be a common process in diverse diseases.

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Acknowledgments

This work was supported by grants from National Institute of Mental Health (RO1 MH057414) and National Institute of Neurological Disorders and Stroke (RO1 NS024760), from the National Institute on Aging (P01 AG00001), and from the Dudley Allen Sargent Research Fund, SAR, Boston University.

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  1. Department of Health Sciences, Boston University, 635 Commonwealth Ave., Boston, MA, 02215, USA

    John C. Fiala, Marcia Feinberg & Helen Barbas

  2. Program in Neuroscience, Boston University, Boston, MA, 02215, USA

    Alan Peters & Helen Barbas

  3. Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA, 02118, USA

    Alan Peters & Helen Barbas

  4. New England Primate Research Center, Harvard Medical School, Boston, MA, 02115, USA

    Helen Barbas

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  1. John C. Fiala
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Fiala, J.C., Feinberg, M., Peters, A. et al. Mitochondrial degeneration in dystrophic neurites of senile plaques may lead to extracellular deposition of fine filaments. Brain Struct Funct 212, 195–207 (2007). https://doi.org/10.1007/s00429-007-0153-1

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