Plasma and serum neurofilament-light levels increase in an age- and pathology-dependent manner in the Arctic mouse model of Alzheimer's disease.

• DOI: 10.1002/alz.056343
• Publication Date: 2021-12-01
• Authors: Nicole D. Schartz; Purnika Selvan; Shu‐Hui Chu; Andrea J. Tenner

Alzheimer's disease (AD) is the most prevalent form of dementia elderly in US. No disease-modifying drugs have been approved, indicating a need for novel targets and relevant biomarkers to follow treatment efficacy. Neurofilament-light (NfL) an intermediate filament protein neurons that increases plasma after injury neurodegeneration, suggesting it may be biomarker neurodegeneration before other symptoms are evident. Here, we measured blood NfL levels Arctic AD mouse compared neuroprotective model which C5aR1 was genetically ablated (C5aR1KO) microglial activation marker CD11c fibrillar plaque load brain.Blood collected via cardiac puncture from WT, Arctic, C5aR1KO, ArcticC5aR1KO at 5, 7, 10, 13 months age processed or serum isolation. The MSD kit used detect NfL. Immunohistochemical detection CD11c-positive microglia ThioS-stained plaques were analyzed by Imaris.Comparison both WT mice demonstrated increased with increasing (p=0.02 0.01, respectively) trend greater vs 7 (p=0.1) (p=0.08) months. In mice, there 44% reduction Interestingly, 10 months, 35% higher than protective effect observed superseded Similarly, increase ThioS lower (44%, 37% hippocampus CONCLUSION: This study modulation can detected therapeutic intervention (i.e. C5aR1KO), changes paralleled load. These data suggest as progression, serve noninvasive tool measure