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Frontotemporal lobar degeneration; Neuropathologic analysis of brain tissue from FTLD-TDP patients. Ubiquitin immunohistochemistry in cases of familial FTLD-TDP demonstrates staining of (a) neurites and neuronal cytoplasmic inclusions in the superficial cerebral neocortex, (b) neuronal cytoplasmic inclusions in hippocampal dentate granule cells, and (c) neuronal intranuclear inclusions in the ...
Alternatively, diseases exhibiting tau pathologies attributed to different and varied underlying causes are termed 'secondary tauopathies'. Some neuropathologic phenotypes involving tau protein are Alzheimer's disease , frontotemporal dementia , progressive supranuclear palsy , and corticobasal degeneration .
The only other known autosomal dominant genetic cause of FTLD-tau is a hypomorphic mutation in VCP which is associated with a unique neuropathology called vacuolar tauopathy. [35] FTD caused by FTLD-TDP43 has numerous genetic causes. Some cases are due to mutations in the GRN gene, also located on chromosome 17.
[12] [17] [18] Detachment of tau from microtubules causes the neuron to lose its ability to sustain itself and thus ultimately it loses function. Hyper-phosphorylation of tau protein was initially thought to be caused by Aβ 42 but since PART cases generally lack senile plaques, other causes were investigated.
The symptoms of this dementia depend on where in the brain the strokes occurred and whether the blood vessels affected were large or small. [13] Repeated injury can cause progressive dementia over time, while a single injury located in an area critical for cognition such as the hippocampus, or thalamus, can lead to sudden cognitive decline. [75]
SD is a clinically defined syndrome but is associated with predominantly temporal lobe atrophy (left greater than right) and hence is sometimes called temporal variant FTLD (tvFTLD). [7] SD is one of the three variants of primary progressive aphasia (PPA), which results from neurodegenerative disorders such as FTLD or Alzheimer's disease .
In some cases, dry macular degeneration can convert to “wet” degeneration, caused by “bleeding or a leaky blood vessel,” that leads to a much more rapid loss of visual acuity, explains ...
However, when tau is hyperphosphorylated, it is unable to bind and the microtubules become unstable and begin disintegrating. The unbound tau clumps together in formations called neurofibrillary tangles. [4] More explicitly, intracellular lesions known as pretangles develop when tau is phosphorylated excessively and on improper amino acid residues.