Morphology and Distribution of TDP-43 Pre-inclusions in Primary Progressive Aphasia

摘要: Diffusely stained phosphorylated 43-kDa TAR DNA-binding protein (TDP-43)-positive "pre-inclusions" have been described. This experiment investigated morphological subtypes of pre-inclusions and their relationship with TDP-43 inclusions in primary progressive aphasia (PPA), a dementia characterized by gradual dissolution language. Brain sections from 5 PPA participants postmortem diagnoses frontotemporal lobar degeneration pathology (FTLD-TDP) were immunohistochemically using an antibody to quantitatively examined for regional hemispheric distribution unbiased stereology. Cortical included smooth, granular/dot-like, or fibrillar staining localization the nucleus, cytoplasm, both. Mature quantified region high low mature inclusion density, contralateral homologs. Regions lower higher densities pre-inclusions, while increasing burden corresponded (p < 0.05). showed significant asymmetry that favored language-dominant hemisphere 0.01), displayed opposite pattern 0.01). Granular-type more abundant 0.05) drove differences 0.02). These results suggest are present greater abundance prior formation inclusions, appear develop through stages into intracytoplasmic, intranuclear aggregates.