TAR DNA binding protein of 43 kDa (TDP-43) plays an important role in the clinical features associated with Alzheimer's disease, as it is strongly associated with memory loss and smaller hippocampal volumes. However, there are important questions that remain unanswered regarding TDP-43, pathological subtype, and clinical features in Alzheimer's disease.
Mayo Clinic researchers, first author Keith Josephs, M.D., performed a clinico-imaging-pathological study to determine whether the frequency of TDP-43 deposition in Alzheimer's disease differs across pathologically defined Alzheimer's disease subtypes (Hippocampal sparing [HpSp]; Typical and Limbic), and to further examine the relationship between TDP-43, pathological subtype, and clinical features in Alzheimer's disease. The study was published in the Annals of Neurology journal.
Researchers identified all cases with pathologically confirmed Alzheimer's disease independent of cognitive status. Neurofibrillary tangle counts were performed using thioflavin-S microscopy in hippocampus and three neocortical regions, and all cases were subtyped: HpSp Alzheimer's disease pathology; Typical Alzheimer's disease pathology; Limbic Alzheimer's disease pathology.
It was discovered that TDP-43 deposition was frequent in Typical (59 percent) and Limbic Alzheimer's disease pathologies (67 percent), but not HpSp Alzheimer's disease pathology (21 percent). The observed associations of TDP-43 with greater memory loss, naming and functional decline, and smaller hippocampal volumes, closest to death, did not differ across Alzheimer's disease pathological subtype.
Based on these results, although the frequency of TDP-43 deposition in Alzheimer's disease varies by pathological subtype, the observed effects of TDP-43 on clinical/MRI features are consistent across pathological subtypes. Clinical presentation in Alzheimer's diseaseis driven by pathological subtype, not by TDP-43.