Considering these aspects, we hypothesized that widespread TDP-43 and UCH-L1 proteinopathy may underlie multifocal neuronal dysfunction that contributes to complex nonmotor phenotypes in autism, including cognitive impairment with prominent frontal executive dysfunction and extrapyramidal signs.
TDP-43 Proteinopathy and ALS: Insights into Disease Mechanisms and Therapeutic Targets.
As illustrated in Figure 1, A through F, neuropathologic examination revealed 4 common pathologies of aging rather than AD neuropathology in this patient with dementia, namely: (1) a TDP-43 proteinopathy involving limbic structures without HS, that is, CARTS; (2) multifocal largeand small-vessel vascular brain injury; (3) Braak stage II--III without amyloid deposition, consistent with PART; and (4) the non-AD tauopathy of argyrophilic grains.
Immunohistochemistry for TDP-43 demonstrated a severe TDP-43 proteinopathy in limbic regions, including neuronal inclusions in hippocampal dentate granule cells and within CA1 in the form of slender neurites.
EXAMPLE 4, SAMPLE AUTOPSY SIGNOUT: * Frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP), Type A, with: *** Severe temporal lobe atrophy, bilateral *** Frontal lobe atrophy, mild *** Hippocampal sclerosis, bilateral, severe *** Neuronal intranuclear ("lentiform") inclusions * Alzheimer disease neuropathology changes, "high", (A2,B3,C1): *** Thal phase for amyloid plaques: 3 (A2) *** Braak and Braak neurofibrillary stage: V (B3) *** CERAD neuritic plaque score: Predominantly sparse (CI) *** No cerebral amyloid angiopathy is identified * No Lewy body disease pathology is identified Comment: FTLD-TDP, Type A, is identified with associated severe TDP-43 proteinopathy, circumscribed atrophy of bilateral anteromedial temporal lobes and bilateral hippocampal sclerosis.
20) In most FTLDs, hippocampal neuronal loss and gliosis is less striking than in AD, unless there is also hippocampal sclerosis, which is most often found in frontotemporal lobar degeneration with TAR DNA-binding protein of 43 kDa (TDP-43) proteinopathy