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Washington University Experience | NEURODEGENERATION | Hippocampal Sclerosis of Aging | 1F Case 1 Denouement
Final Neuropathologic Diagnosis: DLBD Diffuse Lewy body disease (limbic stage); Hippocampal sclerosis; Primary age-related tauopathy (PART); Alzheimer disease neuropathologic change (Low: A1B2C0); TDP-43 neuronal cytoplasmic inclusions in medial temporal lobe; Age-related tau astrogliopathy (ARTAG) ---- Neuropathology Diagnosis Comment: The main neuropathologic findings of this case are diffuse Lewy body disease (DLBD), the pathological correlate of dementia with Lewy bodies (DLB), primary age-related tauopathy, mild TDP-43 proteinopathy (PART), and hippocampal sclerosis. ---- This case displays alpha-synuclein-positive inclusions in the form of Lewy bodies and Lewy neurites in the brainstem, limbic and neocortical areas. This brain is remarkable in that AD pathology is almost entirely absent. A few solitary diffuse beta-amyloid plaques were only found in the frontal and parietal lobes and amygdala. There are no neuritic plaques and neurofibrillary tangles are confined largely to the medial temporal lobe consistent with Braak and Braak neurofibrillary tangle stage IV (range: I-VI) and amyloid stage A (range: A-C). The absence of neuritic plaques and the scarcity of beta-amyloid plaques exclude the neuropathologic diagnosis of AD according to Khachaturian, CERAD, NIA-Reagan Institute and NIA-AA criteria, (ADNC: A1B2C0, “low” degree of AD). Sparse TDP-43-immunoreactive NCIs in the dentate fascia are seen and these have been reported in the context of some older cases of AD and hippocampal sclerosis and independent of frontotemporal lobar degeneration (FTLD), but in this case FTLD was absent. Finally, vascular pathology in the form of mild to focally moderate arteriolosclerosis is present but there are no infarcts. These changes are unlikely to have contributed to the cognitive impairment. In conclusion, in this patient there was evidence of four molecular pathologies: synucleinopathy, minimal beta-amyloidosis, tauopathy, and very modest TDP-43 proteinopathy in addition to mild small vessel disease. Lewy body disease and PART together with hippocampal sclerosis are most likely to explain the major cognitive and motor deficits with a modest contribution from ADNC and ARTAG.
