Levels of plasma neurofilament light and pTau‐181 predict for steeper cognitive decline in Typical AD and Hippocampal‐sparing compared to Limbic‐predominant AD subtype

Background Recent studies suggest plasma neurofilament light (p-NFL) and phosporylated-Tau-181 (p-pTau181) are valuable biomarkers for detecting faster cognitive decline in patients with Alzheimer’s Disease (AD) dementia. Recently, AD subtyping has been used to subgroup into phenotypes possibly different prognoses. The aim of this study was investigate the interaction between p-NFL p-pTau-181 subtypes predict episodic memory. Method In total, 357 non-AD (Aß-) (Cognitive Normal Mild Cognitive Impairment) 73 subjects (Aß+, according mainly Amyloid-PET or -CSF) were selected from Neuroimaging Initiative (ADNI) dataset. Subjects had at least one sample MRI scan. latter subtype (Risacher et al. 2017). subtyped Limbic-predominant (18%), typical (67%) Hippocampal-sparing (15%) subtypes. ADNI_MEM composite score as proxy cognition. Linear mixed models tested up 4.5 years follow (27.7±13.1 months) including time, p-pTau-181. Age, gender, education, ApoE4 status included models. Models incrementally through model comparison (AIC, BIC). final both Result did not differ cognition (-1±0.6 whole group) age (74±8 ys group), but gender. Higher levels Typical showed compared (p<0.05, both), while not. For p-pTau-181, significant stronger separation across all than p-NFL. Combining improved only interactive effects pTau-181 both). Conclusion two progressive (episodic memory), suggesting that late disease onset (contrary subtype), cannot be early detected