Acta Neuropathologica: Different clinical pathology groupings for patients with TDP-43 protein disease.

TAR-DNA binding protein 43 kDa (TDP-43) protein disease is present in up to 50% of the elderly brain and is highly associated with cognitive impairment.
, a working group proposed a classification system for age-related TDP-43 neuropathological changes in encephalopathy (LATE-NC).
term is parallel to the current classification of Alzheimer's disease (AD), where neuropathological changes are called ADNC.
cross-sectional data show that TDP-43 protein lesions occur in the brain in a stereotyped, layered pattern of time and space.
In this hypothetical model, TDP-43 deposits first appear in the amygdala and then in the hippoc mark, and in about 15 percent of older adults, it may develop in the neothal cortical and other brain structures of the frontal leaves, which is the basis for the proposed late NC neuropathological stages.
the specific definitions and characteristics of late NC, ADNC, and frontal temporal lobe degeneration (FTLD-TDP), which is associated with TDP-43 protein disease, there is some controversy in this area.
convincing data suggest that there are parallel or synergetic mechanisms in ADNC and late NC, as these two diseases are usually co-diseases.
, however, many serious ADNC cases lack late NC, and late NC can occur without ADNC (about 75% of the elderly brain has ADNC, with or without a combination of late NC).
: To better understand the clinical and neuropathological characteristics of TDP-43 protein lesions, this paper analyzes data from study volunteers tracked by the National Alzheimer's Coordination Center (NACC) dataset.
all subjects (n-495) autopsies confirmed that TDP-43 protein disease became standard.
subjects received a comprehensive longitudinal clinical assessment for an average of 6.9 years per year before death.
based on the age of death and extensive neuropathological data, the authors tested whether unsuperpted clustering algorithms were able to detect relevant groups of TDP-43 immuno-positive cases.
Although many brains have different pathological states, the authors found four identifiable clusters, the main identification of which was neuropathological changes (ADNC) in age of death and the severity of Alzheimer's disease, especially neurosomalloid plaque density.
Group 1 consisted mainly of cases of pathological diagnosis of temporal lobe degeneration (FTLD-TDP), consistent with the richness of clinical idioms of preterm temporal lobe dementia, including appetite/eating problems, desuppression, and primary sexual adaffles (PPA).
group 2 consisted of elderly TDP-43 encephalopathy (late NC) patients with an elderly edge advantage, with no severe neuritis amyloid plaques.
the second group had a relatively slow cognitive decline.
group 3 and group 4 had severe ADNC-late NC.
, the 4th group was characterized by early onset, fast course of disease, more pathology of Louis, and less lesions of the neo-cortical TDP-43 protein.
Overall, clusters rich in neo-cortical TDP-43 protein lesions (groups 1 and 2) tend to have lower levels of neuritis amyloid plaques, while those who die in older adults (groups 2 and 3) have much less PPA or desuppression, but are more apathetic.
fact, 98% of subjects over the age of 85 who died lacked clinical characteristics of frontal lobe dementia syndrome.
this paper reveals the identifiable subsypes of late NC and emphasizes the importance of age of death in distinguishing between FLD-TDP and late NC.
Katsumata, Y., Abner, E.L., Karanth, S. et al. Distinct clinicopathologic clusters of people with TDP-43 proteinopathy. Acta Neuropathol (2020). Source: MedSci Originals !-- Content Presentation Ends -- !-- To Determine If Login Ends.