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Washington University Experience | NEURODEGENERATION | Alzheimer Disease | Gross Pathology | 6B Case 6 Denouement
Neuro Microscopic Description: ---- Neuronal loss and gliosis are mild to moderate and there is microvacuolation in superficial layers of the cerebral cortex. Diffuse beta-amyloid plaques are frequent and cored plaques are few to moderate in number. Tau immunohistochemistry reveals frequent neurofibrillary tangles (NFT) and some pre-tangles (diffusely immunoreactive neurons), few to frequent neuritic plaques, and frequent neuropil threads; tau-immunoreactive neuritic plaques are difficult to discern due to the numerous neuropil threads and tangles. No pTDP-43-immunoreactive neuronal cytoplasmic inclusions (NCIs) or alpha-synuclein-positive inclusions (Lewy bodies and Lewy neurites) are identified. ---- Neuro Diagnosis Comment: The main neuropathological finding in this case is Alzheimer disease. Diffuse and neuritic beta-amyloid plaques and neurofibrillary tangles are present in distributions and densities consistent with Braak and Braak neurofibrillary tangle stage VI (range: 0-VI) and amyloid stage C (range: A-C). These findings support a neuropathological diagnosis of AD by Khachaturian, CERAD, NIA-Reagan Institute criteria. Using NIA-AA criteria, this case is classified as A3B3C3, indicating that there is a ‘high’ probability that the AD neuropathologic changes explain the dementia. In addition to AD pathology, this case also displays a modest burden of alpha-synuclein positive Lewy bodies and Lewy neurites in the amygdala and olfactory cortex; these are absent from the neocortex and brainstem. Given the absence of alpha-synuclein immunoreactive inclusions in the brainstem, this case is not readily categorized within the staging of Lewy body pathology described by Braak et al. and does not support of idiopathic Parkinson disease or diffuse Lewy body disease. Additionally, the substantia nigra shows only modest neuronal loss. The modest density and distribution of Lewy bodies in this case is most consistent with an entity called 'Alzheimer disease with amygdala Lewy bodies’ (PMID: 16825955). Given its limited distribution, it is unlikely that the Lewy body pathology caused any significant motor or cognitive deficits. Vascular pathology is present in the form of arteriolosclerosis and cerebral amyloid angiopathy. Overall, this vasculopathy is mild and unlikely to have contributed significantly to the clinical phenotype.
