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Washington University Experience | NEURODEGENERATION | Primary Age-Related Tauopathy (PART) | 1F Case 1 Denouement
Neuro Final Diagnosis: Diffuse Lewy body disease (correlate of dementia with Lewy bodies – limbic stage); Primary age-related tauopathy (PART); Argyrophilic grain disease (stage III); Alzheimer disease neuropathologic change (Low: A1, B2, C0); TDP-43 neuronal cytoplasmic inclusions in medial temporal lobe; Age-related tau astrogliopathy (ARTAG) ---- Neuro 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 (PART) and argyrophilic grain disease (AGD). Minor changes include: Alzheimer disease neuropathologic change (ADNC), age-related tau astrogliopathy (ARTAG), mild TDP-43 proteinopathy, and mild small vessel disease. This case displays alpha-synuclein-positive inclusions in the form of Lewy bodies and Lewy neurites in brainstem, limbic and neocortical areas sufficient for a diagnosis of ‘dementia with Lewy bodies’ (limbic stage). This brain is remarkable in that AD pathology is almost entirely absent. There are no neuritic plaques and neurofibrillary tangles are confined to the medial temporal lobe. 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 [Alzheimer diseases neuropathological change (ADNC): A1, B2, C0, where A = beta-amyloid stage, Thal beta-amyloid stage 1/5; B = Braak neurofibrillary tangle stage (range: 0-3); and C = CERAD neuritic plaque stage (range: 0-3). These AD neuropathologic changes indicate a “low” degree of AD neuropathologic change. This case has a constellation of tau-immunoreactive features (grains, pre-tangles, tangles, astrocytes, oligodendroglial coiled bodies, and ‘ballooned’ neurons) variably involving the medial temporal lobe and anterior cingulate gyrus consistent with argyrophilic grain disease, stage 3. In addition, patches of tau-immunoreactive astrocytes are seen, [‘age-related tau astrogliopathy’ (ARTAG)]. TDP-43-immunoreactive NCIs in the medial temporal lobe are seen and these have been reported in the context of some older cases of AD and independent of frontotemporal lobar degeneration (FTLD); in this case FTLD was absent. Finally, vascular pathology in the form of mild 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 TDP-43 proteinopathy in addition to mild small vessel disease. Lewy body disease and PART together are most likely to explain the major cognitive and motor deficits with a modest contribution from AGD, ADNC, ARTAG, and TDP- 43 proteinopathy. (Particular thanks to Dr. Nigel Cairns for this analysis and writeup)
