Abstract
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.