UC Davis

Chapter I introduces the importance and challenges of studying glycosylation. The chapter describes the long-term associations between glycosylation and brain development. However, emphasis is placed in the interplay between protein glycosylation and Alzheimer’s Disease. The chapter further discusses the key aspects of employing mass spectrometry techniques for glycomic and glycoproteomic analysis.

In Chapter II, a comprehensive map of the N-glycome and glycoproteome of the human brain is presented. The study involved four subjects, two with confirmed Alzheimer Disease neuropathology and the remaining two termed non-cognitive impaired. This map involved 11 functional human brain regions per subject.

The research described in Chapter III, resulted from the human brain glycome map findings. This study only focused on three functional brain regions affected differently in the Alzheimer’s Disease pathology. The study design involved higher biological replicates per region and was characterized using a novel nano-liquid chromatography chip-quadrupole-time of flight mass spectrometry (nanoLC-Chip-Q-ToF MS) platform.

The motivation behind Chapter IV, involved the increased demand for the development of novel blood-based biomarkers for early detection, prevention, or intervention in Alzheimer’s Disease. This research sought out to determine whether serum glycopeptide analysis holds potential for identifying novel diagnostics and prognostics of Alzheimer’s Disease. This work used an ultra-high-performance liquid-chromatography triple quadrupole mass spectrometry (UHPLC-QqQ-MS) operated in dynamic multiple reaction monitoring (dMRM) mode to monitor glycopeptides alterations in Alzheimer’s Disease patients.

Together these chapters highlight the powerful application of mass spectrometry techniques in biological and biomarker research discovery.