Plasma biomarkers Aβ42, Aβ40, and tau in Down syndrome dementia

Abstract

AbstractBackgroundAdults with Down syndrome (DS) develop Alzheimer’s disease (AD) brain changes, including excess Aβ42, Aβ40, and tau aggregates, generally by the fifth decade of life, and with time ultimately develop a dementia syndrome. Here we examine the relationship of baseline plasma biomarkers Aβ42, Aβ40, and tau, to dementia status, in adults with DS from a large DS cohort (ADDS funded by NIH grant U01AG051412).MethodsParticipants included 164 adults with DS who provided blood sample for plasma isolation at enrollment baseline, with mean age 50.9±6.9 yr (range 40 to 81), including 92 men (56%) and 72 women (44%), with ethnic distribution 87% white, 6% Hispanic, 4% Asian, 2% black, and 1% Native American. Dementia status was 18% with Dementia, 21% with Mild Cognitive Impairment (MCI), 58% without MCI or dementia, and 2% undetermined. Apolipoprotein E (APOE) status was available for N=157: 71% no e4, 29% ≥1 e4. Plasma Aβ42, Aβ40, and tau were determined using a SIMOA (Quanterix) SR‐X system with Neuroplex‐3 kits.ResultsMean levels (pg/ml) were Aβ42 20.3±5.8 (range 9.0‐47.0) , Aβ40 468±116 (163‐896), and tau 4.78±2.85 (1.52‐20.46), with derived ratios Aβ42/Aβ40 0.044±0.010 (0.018‐0.101) and tau/Aβ42 0.236±0.124 (0.065‐1.191). Neither AB42 nor AB40 levels, nor tau/AB42 ratio correlated with age, although the AB42/AB40 ratio did show some decline with age (r = .16; p = 0.04). Dementia status, adjusted for age, did not significantly relate to baseline Aβ42, Aβ40 or Aβ42/Aβ40 ratio, but did relate to tau/Aβ42 ratio. The group of individuals with DS and MCI or Dementia had significantly greater tau/Aβ42 ratios (p= 0.001), than the group without, as did the groups just with MCI (p = 0.012), or just with dementia (p = 0.008), when adjusted for age and sex. These relationships were preserved when additionally adjusting for ethnicity and presence of APOE e4 allele, which itself was significantly related to dementia status.ConclusionsWhile cerebrospinal fluid measures are the gold standard for assessing Alzheimer’ pathology, these results suggest that in persons with DS, plasma measurements of Aβ42 and tau using the SIMOA technique may allow biomarker confirmation of Alzheimer’s dementia.