Table of Contents
Washington University Experience | NEURODEGENERATION | Alzheimer Disease | Gross Pathology | 7B Case 7 Denouement
Neuro Microscopic Description: Neuronal loss and gliosis are moderate to severe with focal superficial microvacuolation. Frequent beta-amyloid plaques, frequent neurofibrillary tangles and neuritic plaques are noted. Tau immunohistochemistry also reveals diffusely tau-immunoreactive neurons (interpreted as indicating a pre-tangle stage). No alpha-synuclein-positive inclusions (Lewy bodies) are seen and no pTDP-43-immunoreactive neuronal cytoplasmic inclusions (NCIs) are identified. There is moderate to focally severe cerebral amyloid angiopathy. Both the amygdala and entorhinal cortex contain several pTDP-43-immunoreactive NCIs and dystrophic neurites. There are frequent beta-amyloid plaques, numerous tangles and neuritic plaques but no Lewy bodies and no Pick bodies. ---- Neuro Diagnosis Comment: The main neurodegenerative finding of this case is Alzheimer disease. Supporting a diagnosis of AD, beta-amyloid plaques and neurofibrillary tangles are present in distributions and densities consistent with Braak and Braak neurofibrillary tangle stage V (range: I-VI) and amyloid stage C (range: A-C). These lesions, including neuritic plaques, indicate a neuropathological diagnosis of AD according to the Khachaturian, CERAD, and NIA-Reagan Institute criteria. In the more recent National Institute on Aging-Alzheimer Association (NIA-AA) criteria, this case has neuropathological change consistent with AD (A3B3C3). In addition to diagnostic features of AD, this case also shows isolated pTDP-43- immunoreactive NCIs in the medial temporal lobe and adjacent structures. Neuronal cytoplasmic inclusions (NCI) containing pTDP-43 protein represent hallmark features of several diseases, (e.g. amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) and have also been described as a co-morbidity in other more common diseases, including Alzheimer disease. The distribution of pTDP-43 positive NCIs seen here in the medial temporal lobe, in combination with the AD pathology described above, is consistent with an entity, tentatively called ‘AD with limbic pTDP-43 proteinopathy' (PMID: 18401022). The contribution of these TDP-43 positive inclusions to cognitive impairment in this context is not entirely clear, but has been reported in one study. There was no evidence of any other neurodegenerative disease. Finally, vascular pathology, in the form of moderate to severe CAA, and arteriolosclerosis, is an additional finding in this case. Together, these vascular changes may have had a modest influence on cognition.
