6 research outputs found
The G55R mutation increases the ability of 4R tau but not 3R tau to nucleate microtubule assembly.
<p>(A) Microtubule assembly in reactions containing a 1∶30 tau:tubulin dimer molar ratio were assayed by light scattering as a function of time. (B) Co-sedimentation assays demonstrate that the G55R mutation does not affect the ability of tau to assemble MT mass at steady-state, nor does it affect the ability of tau to bind to microtubules. Statistical significance was determined by comparing each mutant to its corresponding WT using two-tailed t-tests. Data in both panels represent the mean ± SEM from three independent experiments.</p
Schematic map of the six CNS tau isoforms.
<p>Exons 2 (E2), 3 (E3) and 10 (E10) are alternatively spliced to generate all six possible combinations. Arrowheads denote the position of the G55R mutation, present in four of the six isoforms. R1, R2, R3 and R4 denote the four imperfect repeats in the MT binding region.</p
A. The family tree of the affected family shows the pattern of inheritance.
<p>The proband is the black oval on the left side of the figure (II:1), marked with an arrow. Tau haplotypes of sequenced individuals are also noted. “aoo” corresponds to age of onset; “aod” corresponds to age of death; black filling indicates persons possessing the G55R mutation; gray filling corresponds to diagnosed dementia of unknown origin (presumed to be G55R but inadequate medical records exist). Proband's son III:1 (from first marriage) is 36 years old and a carrier of G55R. Proband's second son III:2 (from second marriage) is 31 and also a G55R carrier. The other two sons (III:3 and III:4; from the second marriage) are not G55R carriers and are 29 and 28 years old. <b>B. The tau sequence in the region of the G55R mutation is extremely highly conserved across species lines.</b> The glycine at position 55 is completely conserved in seven species ranging from humans to lizards. Color coding emphasizes conserved nature of acidic (red), basic (blue), hydrophilic/polar (orange), hydrophobic (green) and proline (peach) positions.</p
Results of MRI and SPECT examination of a control subject.
<p>Magnetic Resonance Imaging and Single Photon Emission Computed Tomography demonstrating the normal scans of a control, age-matched patient with no signs of any neurodegenerative disorder.</p
Results of MRI and SPECT examinations of the proband.
<p>Magnetic Resonance Imaging revealed marked cortical and subcortical atrophy within both occipital and parietal lobes bilaterally. The atrophy was less pronounced in the frontal and temporal lobes, and the hippocampal structures of the temporal lobes were mostly preserved. Single Photon Emission Computed Tomography demonstrated severe hypoperfusion within the parietal, occipital and temporal lobes bilaterally.</p
Analysis of visuospatial dysfunction of the patient.
<p>Patient's drawings in the context of drawings by a patient with semantic dementia. (SD) scoring 19 in MMSE were presented. A) flowers drawn by the patients from memory: A1) PCA patient, A2) SD patient; B) model, C) patients' copy: C1) PCA patient, C2) SD patient. Copying pictures and drawing to command indicated severe optic ataxia and partial simultanognosia. The test was performed at first neuropsychological assessment. During the second assessment (six months later) the patient was unable to draw even simple patterns and presented with complete simultanognosia.</p