Amyloid beta impairs mitochondrial anterograde transport and degenerates synapses in Alzheimer's disease neurons

Marcus J. Calkins, P (Hemachandra) Reddy

    Research output: Contribution to journalArticle

    126 Citations (Scopus)

    Abstract

    Loss of synapses and synaptic damage are the best correlates of cognitive decline identified in patients with Alzheimer's disease (AD), and mitochondrial oxidative damage and synaptic pathology have been identified as early events in the progression of AD. The progressive accumulation of amyloid beta (Aβ) in synapses and synaptic mitochondria are hypothesized to cause synaptic degeneration and cognitive decline in patients with AD. However, the precise mechanistic link between Aβ and mitochondria is not well understood. The purpose of this study was to better understand the effects of Aβ on mitochondrial axonal transport and synaptic alterations in AD. Using mouse hippocampal neurons and Aβ25-35 peptide, we studied axonal transport of mitochondria, including mitochondrial motility, mitochondrial length and size, mitochondrial index per neurite, and synaptic alterations of the hippocampal neurons. In the PBS-treated neurons, 36.4±4.7% of the observed mitochondria were motile, with 21.0±1.3% moving anterograde and 15.4±3.4% moving retrograde and the average speed of movement was 12.1±1.8μm/min. In contrast, in the Aβ-treated neurons, the number of motile mitochondria were significantly less, at 20.4±2.6% (P25-35 peptide impairs axonal transport of mitochondria in AD neurons. In the Aβ-treated neurons, the average speed of motile mitochondria was also less, at 10.9±1.9μm/min, and mitochondrial length was significantly decreased. Further, synaptic immunoreactivity was also significantly less in the Aβ-treated neurons relative to the PBS-treated neurons, indicating that Aβ affects synaptic viability. These findings suggest that, in neurons affected by AD, Aβ is toxic, impairs mitochondrial movements, reduces mitochondrial length, and causes synaptic degeneration.

    Original languageEnglish (US)
    Pages (from-to)507-513
    Number of pages7
    JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
    Volume1812
    Issue number4
    DOIs
    StatePublished - Apr 2011

    Fingerprint

    Amyloid
    Synapses
    Alzheimer Disease
    Neurons
    Mitochondria
    Axonal Transport
    Mitochondrial Size
    Peptides
    Poisons
    Neurites
    Pathology

    Keywords

    • Alzheimer's disease
    • Amyloid beta
    • Axonal transport
    • Mitochondria
    • Mitochondrial dynamics
    • Mitochondrial fission

    ASJC Scopus subject areas

    • Molecular Biology
    • Molecular Medicine

    Cite this

    Amyloid beta impairs mitochondrial anterograde transport and degenerates synapses in Alzheimer's disease neurons. / Calkins, Marcus J.; Reddy, P (Hemachandra).

    In: Biochimica et Biophysica Acta - Molecular Basis of Disease, Vol. 1812, No. 4, 04.2011, p. 507-513.

    Research output: Contribution to journalArticle

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