The role of Tau, amyloid-β and neuroinflammation in the association between cognition and white matter hyperintensities in a southeast Asian cohort

Elevated Glial Fibrillary Acidic Protein (GFAP) is associated with increased Phosphorylated Tau 181 (pTau181) induced neurodegeneration in Alzheimer's Disease. However, the role of GFAP and pTau181 in vascular/mixed dementias requires elucidation within the Southeast Asian context, where their burden is considerable. Population based cross-sectional study. Biomarkers and Cognition Study, Singapore (BIOCIS). Baseline data from n = 583 (40.3 % male), non-demented but at risk, Southeast Asian community participants, were included in this analysis. All participants displayed cognitive symptoms on the Subjective Memory Complaints Questionnaire, although they may or may not have objective cognitive deficits and did not meet the criteria for dementia as per the DSM - 5. Neuropsychological assessments for executive function evaluation, volumetric White Matter Hyperintensities (WMH) measurement and plasma biomarker expression, were determined in non-demented but at risk, Southeast Asian research participants. Partial correlation analysis demonstrated variable associations. Simple moderation analysis revealed the ability for plasma biomarkers to influence the relationship between executive function and WMH. WMH burden positively correlated to Neurofilament-Light (NfL) and pTau181. Executive function and processing speed negatively correlated to WMH burden. GFAP positively correlated to pTau181 and negatively correlated to executive function. NfL, GFAP, pTau181, and Amyloid beta 42/Amyloid beta 40 (Aβ42/Aβ40) ratio independently moderated, the relationship between executive function/processing speed and WMH burden. Inflammatory mechanisms represented by GFAP were linked to tau pathology and WMH and also moderated the association between WMH on cognitive performance.