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Washington University Experience | NEURODEGENERATION | Hippocampal Sclerosis of Aging | 2F Case 2 Denouement
Final Neuropathologic Diagnoses: Alzheimer disease neuropathologic change (High: A3, B3, C3); Diffuse Lewy body disease (limbic predominant); Hippocampal sclerosis; 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 Alzheimer disease neuropathologic change (ADNC), diffuse Lewy body disease (mainly in brainstem and limbic areas), hippocampal sclerosis, and modest TDP-43 proteinopathy in the medial temporal lobe. Likely to have contributed to cognitive decline in this patient, is severe Alzheimer disease neuropathologic change (ADNC) by NIA-AA criteria A3B3C3, High likelihood). A significant finding in this case relevant to cognitive impairment is severe neuronal loss within the subiculum and CA1 subfield of the hippocampus, supporting the diagnosis of hippocampal sclerosis (HS). Also consistent with this diagnosis, a few TDP-43-immunoreactive NCIs are present in the dentate fascia and medial temporal lobe, without co-incident features of frontotemporal lobar degeneration (FTLD). This brain also shows alpha-synuclein-positive Lewy bodies and Lewy neurites in the brainstem and limbic areas with only very modest involvement of neocortical areas. As the participant had dementia and hallucinations, the clinicopathologic entity called ‘dementia with Lewy bodies’ may be applied, and given the distribution of Lewy bodies, this is consistent with a limbic stage. The relatively well-preserved substantia nigra indicates that the Lewy body disease did not impact significantly on the motor areas and no parkinsonism was noted. In the staging of Lewy body pathology in Parkinson disease according to Braak et al., this case may be rate stage 4 (range: 1-6). Also observed in this case are multiple patches of tau-immunoreactive ‘thorny’ astrocytes in the white matter near the frontal lobe, temporal lobe, occipital lobe, and brainstem, consistent with a recently described entity called age-related tau astrogliopathy (ARTAG). Finally, vascular pathology in the form of mild cerebral amyloid angiopathy (CAA) and mild to moderate arteriolosclerosis is present but no infarcts were seen in the left hemibrain. It is unlikely that these changes contributed to the cognitive impairment. In conclusion, in this patient there was evidence of four molecular pathologies (tauopathy, beta-amyloidosis, TDP-43 proteinopathy, and synucleinopathy) in addition to small vessel disease. ADNC, Lewy body disease, and hippocampal sclerosis are most likely to explain the cognitive deficits. One might ask what role AD had in hippocampal pathology since there are pieces of PHF immunoreactive elements in regions of marked neuronal loss in CA1.
