Truncated tau deregulates synaptic markers in rat model for human tauopathy

Synaptic failure and neurofibrillary degeneration are two major neuropathological substrates of cognitive dysfunction in Alzheimer’s disease (AD). Only a few studies have demonstrated a direct relationship between these two AD hallmarks. To investigate tau mediated synaptic injury we used rat model of tauopathy that develops extensive neurofibrillary pathology in the cortex. Using fractionation of cortical synapses, we identified an increase in endogenous rat tau isoforms in presynaptic compartment, and their mis-sorting to the postsynaptic density (PSD). Truncated transgenic tau was distributed in both compartments exhibiting specific phospho-pattern that was characteristic for each synaptic compartment. In the presynaptic compartment, truncated tau was associated with impairment of dynamic stability of microtubules which could be responsible for reduction of synaptic vesicles. In the PSD, truncated tau lowered the levels of neurofilaments. Truncated tau also significantly decreased the synaptic levels of Aβ40 but not Aβ42. These data show that truncated tau differentially deregulates synaptic proteome in pre- and postsynaptic compartments. Importantly, we show that alteration of Aβ can arise downstream of truncated tau pathology.

• Publication year

  2015

• Venue

  Frontiers in Cellular Neuroscience

• Publication date

  2015-02-23

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.3389/fncel.2015.00024PMID 25755633PMCID 4337338
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• Truncated tau decreased synaptic Aβ40 but not Aβ42.

  Confidence 0.94

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewjihoonc (k5vuy3tzcm) reviewGahyoun (29ua5897xm) review
• In the postsynaptic density (PSD), truncated tau lowered neurofilament levels.

  Confidence 0.95

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewjihoonc (k5vuy3tzcm) reviewGahyoun (29ua5897xm) review
• In the presynaptic compartment, truncated tau impaired microtubule dynamic stability and was linked to a reduction in synaptic vesicles.

  Confidence 0.91

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewjihoonc (k5vuy3tzcm) reviewGahyoun (29ua5897xm) review
• Truncated transgenic tau showed compartment-specific phospho-patterns in both the presynaptic compartment and the postsynaptic density (PSD).

  Confidence 0.93

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewjihoonc (k5vuy3tzcm) reviewGahyoun (29ua5897xm) review
• Endogenous rat tau isoforms were enriched in the presynaptic compartment and mis-sorted to the postsynaptic density (PSD).

  Confidence 0.96

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewjihoonc (k5vuy3tzcm) reviewGahyoun (29ua5897xm) review

• aβ40

  peptides

  The 40-amino-acid amyloid-beta peptide measured in synaptic fractions.

  Aliases: amyloid-beta 40, beta-amyloid 40

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewjihoonc (k5vuy3tzcm) reviewGahyoun (29ua5897xm) review
• aβ42

  peptides

  The 42-amino-acid amyloid-beta peptide measured in synaptic fractions.

  Aliases: amyloid-beta 42, beta-amyloid 42

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewjihoonc (k5vuy3tzcm) reviewGahyoun (29ua5897xm) review
• endogenous rat tau isoforms

  protein isoforms

  The native rat tau isoforms detected in cortical synaptic compartments.

  Aliases: native rat tau, rat tau isoforms

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewjihoonc (k5vuy3tzcm) reviewGahyoun (29ua5897xm) review
• microtubule dynamic stability

  cellular processes

  The stability of microtubule assembly and turnover within the presynaptic compartment.

  Aliases: microtubule stability

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewjihoonc (k5vuy3tzcm) reviewGahyoun (29ua5897xm) review
• neurofilaments

  protein complexes

  Neuronal intermediate filament proteins measured in the postsynaptic fraction.

  Aliases: NF proteins

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewjihoonc (k5vuy3tzcm) reviewGahyoun (29ua5897xm) review
• postsynaptic density (psd)

  synaptic structures

  The postsynaptic protein-rich synaptic specialization isolated from cortical synapses.

  Aliases: PSD, postsynaptic density

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewjihoonc (k5vuy3tzcm) reviewGahyoun (29ua5897xm) review
• presynaptic compartment

  cellular compartments

  The presynaptic side of cortical synapses examined as a separate synaptic fraction.

  Aliases: presynaptic side, presynaptic fraction

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewjihoonc (k5vuy3tzcm) reviewGahyoun (29ua5897xm) review
• synaptic vesicles

  cellular components

  Presynaptic vesicles that store neurotransmitter for release at the synapse.

  Aliases: vesicles

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewjihoonc (k5vuy3tzcm) reviewGahyoun (29ua5897xm) review
• truncated tau

  protein fragments

  A transgenic tau fragment present in the rat tauopathy model and analyzed in synaptic fractions.

  Aliases: tau truncation product, truncated transgenic tau

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewjihoonc (k5vuy3tzcm) reviewGahyoun (29ua5897xm) review

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