Purpose: Positron Emission Tomography (PET) can support a diagnosis of neurodegenerative disorder by identifying disease-specific pathologies. Our aim was to investigate the feasibility of using activity reduction in clinical [¹⁸F]FE-PE2I and [¹¹C]PiB PET/CT scans, simulating low injected activity or scanning time reduction, in combination with AI-assisted denoising. Methods: A total of 162 patients with clinically uncertain Alzheimer's disease underwent amyloid [¹¹C]PiB PET/CT and 509 patients referred for clinically uncertain Parkinson's disease underwent dopamine transporter (DAT) [¹⁸F]FE-PE2I PET/CT. Simulated low-activity data were obtained by random sampling of 5% of the events from the list-mode file and a 5% time window extraction in the middle of the scan. A three-dimensional convolutional neural network (CNN) was trained to denoise the resulting PET images for each disease cohort. Results: Noise reduction of low-activity PET images was successful for both cohorts using 5% of the original activity with improvement in visual quality and all similarity metrics with respect to the ground-truth images. Clinically relevant metrics extracted from the low-activity images deviated < 2% compared to ground-truth values, which were not significantly changed when extracting the metrics from the denoised images. Conclusion: The presented models were based on the same network architecture and proved to be a robust tool for denoising brain PET images with two widely different tracer distributions (delocalized, ([¹¹C]PiB, and highly localized, [18F]FE-PE2I). This broad and robust application makes the presented network a good choice for improving the quality of brain images to the level of the standard-activity images without degrading clinical metric extraction. This will allow for reduced dose or scan time in PET/CT to be implemented clinically.