NOVEL BIOMARKERS AND LIPIDS DYSREGULATION IN NEURODEGENERATIVE AND VASCULAR DEMENTIAS

Abstract

The main aim of this thesis is to identify blood-based biomarkers which reflect the diversity of pathologies in dementia. We demonstrated in a Singapore-based cohort of Alzheimer’s dementia (AD) and vascular cognitive impairment patients, that plasma P-tau181/Aβ42 ratio outperformed P-tau181 alone, demonstrating the best performance in detecting elevated brain amyloid (Aβ+) and discriminating between Aβ+ AD and Aβ− vascular dementia patients. Besides, we showed that white matter hyperintensities (WMH; a marker of cerebrovascular disease) and medial temporal lobe atrophy scores were independently associated with plasma neurofilament light chain (NfL), suggesting that in elderly populations with high WMH burden, elevated plasma NfL may be reflective of vascular and non-vascular pathological correlates of neurodegeneration. Moreover, we explored novel biomarker candidates which are associated with neuroinflammation and synaptic function, namely transforming growth factor β and docosahexaenoic acid, in a neuropathologically characterized cohort of AD, dementia with Lewy bodies and Parkinson’s disease dementia patients.