Edison, PaulAllehyany, Bshaier2023-11-072023-11-072023-11-01https://hdl.handle.net/20.500.14154/69580Alzheimer’s disease (AD) biomarkers amyloid-β and tau aggregates have not been effective AD therapeutics, and it is important to investigate other biomarkers for AD to identify novel therapeutic targets that slow disease progression. Glial cell activation markers in the cerebrospinal fluid have recently been associated with AD, especially the astroglial activation marker chitinase-3-like protein 1 (YKL-40) and the microglial activation marker soluble triggering receptor expressed on myeloid cells 2 (sTREM2). Another cerebrospinal fluid marker that has been recently associated with AD is the synaptic dysregulation marker growth associated protein 43 (GAP-43). Despite being associated with amyloid-β and tau pathology, the role of these biomarkers in AD-associated temporoparietal glucose hypometabolism and reductions in grey matter volume is still unclear. This study aimed to investigate the associations between cerebrospinal fluid YKL-40, sTREM2, and GAP-43 and brain glucose hypometabolism and reductions in grey matter volume. Participants (n = 385) were grouped into four conditions: AD, amyloid-positive mild cognitive impairment (MCI), amyloid-negative MCI, and controls. Regional analysis and voxel-level linear regression revealed that YKL-40 could predict temporoparietal glucose hypometabolism in amyloid-positive groups, and that GAP-43 is predictive of different patterns of hypometabolism in the AD group. Only sTREM2 and YKL-40 predicted reduced grey matter volume, but YKL-40 predicted earlier cognitive decline. YKL-40 may be more sensitive to earlier stages of cognitive decline in amyloid-positive participants than the other markers, possibly due to amyloid-induced neuroinflammation and neurodegeneration. However, correlational studies can only give indirect conclusions and future studies are needed to identify direct effects of neuroinflammation and synaptic loss on YKL-40 levels using cell cultures.40en-USYKL-40Alzheimer's diseaseGlucose hypometabolismThesis