Alzheimers Dement. 2023 May 22. doi: 10.1002/alz.13157. Online ahead of print.
ABSTRACT
INTRODUCTION: Understanding longitudinal plasma biomarker trajectories relative to brain amyloid changes can help devise Alzheimer’s progression assessment strategies.
METHODS: We examined the temporal order of changes in plasma amyloid-β ratio ( A β 42 / A β 40 ${{rm A}beta }_{42}/{{rm A}beta }_{40}$ ), glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and phosphorylated tau ratios ( p-tau181 / A β 42 $text{p-tau181}/mathrm{A}{beta}_{42}$ , p-tau231 / A β 42 $text{p-tau231}/mathrm{A}{beta}_{42}$ ) relative to 11 C-Pittsburgh compound B (PiB) positron emission tomography (PET) cortical amyloid burden (PiB-/+). Participants (n = 199) were cognitively normal at index visit with a median 6.1-year follow-up.
RESULTS: PiB groups exhibited different rates of longitudinal change in A β 42 / A β 40 ( β = 5.41 × 10 – 4 , SE = 1.95 × 10 – 4 , p = 0.0073 ) ${{rm A}beta }_{42}/{{rm A}beta }_{40} ( {beta = 5.41 times {{10}}^{ – 4},{rm{ SE }} = 1.95 times {{10}}^{ – 4}, p = 0.0073} )$ . Change in brain amyloid correlated with change in GFAP (r = 0.5, 95% CI = [0.26, 0.68]). The greatest relative decline in A β 42 / A β 40 ${{rm A}beta }_{42}/{{rm A}beta }_{40}$ (-1%/year) preceded brain amyloid positivity by 41 years (95% CI = [32, 53]).
DISCUSSION: Plasma A β 42 / A β 40 ${{rm A}beta }_{42}/{{rm A}beta }_{40}$ may begin declining decades prior to brain amyloid accumulation, whereas p-tau ratios, GFAP, and NfL increase closer in time. HIGHLIGHTS Plasma A β 42 / A β 40 ${{rm A}beta }_{42}/{{rm A}beta }_{40}$ declines over time among PiB- but does not change among PiB+. Phosphorylated-tau to Aβ42 ratios increase over time among PiB+ but do not change among PiB-. Rate of change in brain amyloid is correlated with change in GFAP and neurofilament light chain. The greatest decline in A β 42 / A β 40 ${{rm A}beta }_{42}/{{rm A}beta }_{40}$ may precede brain amyloid positivity by decades.
PMID:37216632 | DOI:10.1002/alz.13157
