Ncmp-15. amyloid-beta and tau-pathology in the glioma vicinity
Neuro-oncology(2023)
摘要
With aging societies the incidences of brain cancer and neurodegenerative disease are increasing. Although biological associations were suggested between glioma and Alzheimer's disease (AD), the rate of comorbidity is ill-defined. We here screened the tumor-adjacent cortex of a representative patient cohort for tau and Amyloid-beta deposits and correlated the results with imaging biomarkers. A total of 290 patients (37 astrocytoma, IDH-mutant, CNS-WHO grades 2-4, median-age: 39; 48 oligodendroglioma, IDH-mutant and 1p-19q-co-deleted, CNS-WHO grades 2-3, median-age: 50; 205 glioblastoma, IDH-wildtype, median-age: 65) were included. Whole-slide quantifications were performed using a digital pathology pipeline based on Matlab and QuPath codes. For a subset of 48 patients with glioblastoma 280 longitudinal MRI volumes were available for segmentation and volumetric analysis of tumor ipsi- and contralateral hippocampuses. Overall, 160 patients (55%) displayed Amyloid-beta and/or tau-pathology in tumor-adjacent cortex. AD protein deposits correlated significantly with age (p< 0.001), and showed topographic variability across brain regions. Amyloid-beta plaques were commonly observed in the occipital cortex in glioblastoma (50%, n= 10/20), while tau-pathology was commonest in the temporal lobe in both IDH-mutant and -wildtype tumors (71%, n= 10/14; 56% n= 44/79). Remarkably, isolated tau-pathology was more prevalent in IDH-mutant glioma (48% vs. 18%, p< 0.001, median age: 45). Median cell density in tumor-infiltrated cortex was highest in glioblastoma (1895 cells/mm²), and associated with reduced neuronal counts and AD protein deposits (p< 0.001). In glioblastoma, hippocampal atrophy correlated with AD-type pathology at time of diagnosis and remained stable during follow-up in the majority of patients. In sum, our data suggests frequent co-morbidity of glioma and AD-type pathology, which increases with age. Isolated tau-pathology was more pronounced in IDH-mutant tumors. In tumor-adjacent cortex, increased tumor cell infiltration paralleled neuronal loss and diminished AD-type pathology.
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关键词
amyloid-beta,tau-pathology
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