Independent associations of plasma Aβ42 and plasma neurofilament light with white matter hyperintensity volume in non‐demented older individuals

Background Plasma biomarkers have potential to capture features of Alzheimer’s disease (AD)-related pathophysiology, but less is known about how they might associate with an imaging measure cerebral small vessel (cSVD). The present study examined independent and combined associations plasma markers AD pathology (Aβ42, P-tau181), axonal damage (neurofilament light [NfL]), astrocytic activation (glial fibrillary acidic protein [GFAP]) white matter hyperintensity (WMH) volume in adults without dementia. Method Aβ42, P-tau181, NfL, GFAP (Quanterix Simoa) were measured 151 older dementia (124 cognitively unimpaired, 27 mild cognitive impairment; aged 52 - 91, 57% female, 95% non-Hispanic white) who underwent MRI T2-weighted FLAIR. Controlling for age, sex, APOE genotype, intracranial volume, linear regressions first WMH as a function each biomarker separately, next model interactive effects associated from the individual models. Result In models, higher volumes lower Aβ42 (β = -0.17, p 0.032, R2 19.4%) NfL concentrations 0.21, 0.013, 20.3%). P-tau181 -0.015, 0.851) 0.05, 0.593) not significantly volume. did demonstrate interaction both remained independently (Aβ42: β -0.19, 0.015; NfL: 0.24, 0.005; 22.7%). No significant interactions between other found. Conclusion burden cSVD quantified by load on non-demented adults. As non-specific marker injury, may utility studies brain degeneration related cSVD. Future are warranted identify factors that be mediating effect amyloid WMH.