Deep clinical and neuropathological phenotyping of Pick disease

ObjectiveTo characterize sequential patterns of regional neuropathology and clinical symptoms in a well‐characterized cohort of 21 patients with autopsy‐confirmed Pick disease. MethodsDetailed neuropathological examination using 70μm and traditional 6μm sections was performed using thioflavin‐S staining and immunohistochemistry for phosphorylated tau, 3R and 4R tau isoforms, ubiquitin, and C‐terminally truncated tau. Patterns of regional tau deposition were correlated with clinical data. In a subset of cases (n = 5), converging evidence was obtained using antemortem neuroimaging measures of gray and white matter integrity. ResultsFour sequential patterns of pathological tau deposition were identified starting in frontotemporal limbic/paralimbic and neocortical regions (phase I). Sequential involvement was seen in subcortical structures, including basal ganglia, locus coeruleus, and raphe nuclei (phase II), followed by primary motor cortex and precerebellar nuclei (phase III) and finally visual cortex in the most severe (phase IV) cases. Behavioral variant frontotemporal dementia was the predominant clinical phenotype (18 of 21), but all patients eventually developed a social comportment disorder. Pathological tau phases reflected the evolution of clinical symptoms and degeneration on serial antemortem neuroimaging, directly correlated with disease duration and inversely correlated with brain weight at autopsy. The majority of neuronal and glial tau inclusions were 3...
Source: Annals of Neurology - Category: Neurology Authors: Tags: Research Article Source Type: research