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Washington University Experience | NEURODEGENERATION | Lewy Body Disease (LBD) | 4 LBD - Gross Pathology - LBD-Dementia with AD | 1B Case 1 Denouement
Neuro Final Diagnosis: Diffuse Lewy body disease; Alzheimer’s disease Neuropathologic Change (ADNC, NIA-AA, A3,B3,C3); TDP-43 proteinopathy in medial temporal lobe, mild ---- Neuro Diagnosis Comment: The main neuropathological findings of this case are diffuse Lewy body disease (pathological correlate of dementia with Lewy bodies) and Alzheimer's disease. Other minor pathologies include modest TDP-43 proteinopathy and modest small vessel disease. Frequent beta-amyloid plaques, frequent neurofibrillary tangles, and few to focally frequent neuritic plaques are present in distributions and densities consistent with AD using criteria of Khachaturian, CERAD, NIA-Reagan and NIA-AA (A3,B3,C3). This case displays alpha-synuclein-positive inclusions in the form of Lewy bodies and Lewy neurites in brainstem, limbic, and neocortical areas. The density and distribution of these lesions are sufficient to meet the criteria for ‘dementia with Lewy bodies (DLB)’ and given the distribution of Lewy bodies this is consistent with a neocortical stage. In the staging of Lewy body pathology in Parkinson’s disease according to Braak et al., this case is stage 6 (range: 1-6). The distribution of TDP-43 positive NCIs seen here in the temporal lobe and adjacent limbic areas, in combination with the AD pathology described above, is consistent with ‘AD with limbic TDP-43 proteinopathy'. The contribution of these few TDP-43 positive inclusions to cognitive impairment in this context is not entirely clear. Finally, vascular pathology in the form of mild to moderate arteriolosclerosis was present. In conclusion, in this Participant there is evidence of four molecular pathologies: beta-amyloidosis, tauopathy, synucleinopathy, and TDP-43 proteinopathy.
