Blood Beta-Amyloid and Tau in Down Syndrome: A Comparison with Alzheimer’s Disease

Abstract

Background: Changes in β-amyloids (Aβ) and tau proteins have been noted in patients with Alzheimer’s disease (AD) and patients with both Down syndrome (DS) and AD. However, reports of changes in the early stage of regression, such as behavioral and psychological symptoms of dementia (BPSD), in DS are sparse.Methods: Seventy-eight controls, 62 patients with AD, 35 with DS and 16 with DS with degeneration (DS_D), including 9 with BPSD and 7 with dementia, were enrolled. The levels of β-amyloids 40 and 42 (Aβ-40, Aβ-42) and tau protein in the blood were analyzed using immunomagnetic reduction (IMR). The Adaptive Behavior Dementia Questionnaire (ABDQ) was used to evaluate the clinical status of the degeneration.Results: The Aβ-40 and tau levels were higher and the Aβ-42 level and Aβ-42/Aβ-40 ratio were lower in DS than in the controls (all p < 0.001). Decreased Aβ-40 and increased Aβ-42 levels and Aβ-42/40 ratios were observed in DS_D compared with DS without degeneration (all p < 0.001). The ABDQ score was negatively correlated with the Aβ-40 level (ρ = −0.556) and the tau protein level (ρ = −0.410) and positively associated with the Aβ-42 level (ρ = 0.621) and the Aβ-42/40 ratio (ρ = 0.544; all p < 0.05).Conclusions: The Aβ-40 and Aβ-42 levels and the Aβ-42/Aβ-40 ratio are considered possible biomarkers for the early detection of degeneration in DS. The elevated Aβ-40 and tau levels in DS may indicate early neurodegeneration. The increased Aβ-42 in DS_D may reflect the neurotoxicity of Aβ-42. The paradox of the tau decreases in DS_D could be explained by a burnout phenomenon during long-term neurodegeneration. The different patterns of the plasma beta amyloids and tau protein may imply a different pathogenesis between DS with degeneration and AD in the general population, in spite of their common key pathological features.

Search for Alzheimer's Disease Biomarkers in Blood Cells: Hypotheses-Driven Approach

“…Exposure of RBCs exposed to Aβ on the luminal surface of cerebral microvessels induces the erythrocytes' adhesion to endothelial cells and affects endothelial functionality [68] [69]. In agreement with these notions, Down syndrome patients with elevated Aβ levels in blood plasma were reported to have a greater risk of developing AD [70,71].…”

“…Four modified morphologies of RBCs triggered by Aβ binding were suggested to indicate AD progression [69]. In agreement with these notions, Down syndrome patients with elevated Aβ levels in blood plasma were reported to have a greater risk of developing AD [70,71].…”

“…Exposure of RBCs exposed to Aβ on the luminal surface of cerebral microvessels induces the erythrocytes' adhesion to endothelial cells and affects endothelial functionality [68] [69]. In agreement with these notions, Down syndrome patients with elevated Aβ levels in blood plasma were reported to have a greater risk of developing AD [70,71].Oxidative stress & altered energy production in RBCs Aβ binding induces oxidative injury to RBCs and causes the accumulation of phospholipid hydroperoxides, a specific marker for RBC membrane oxidative injury [72]. Moreover, an inverse relationship was seen between RBC concentrations of phospholipid hydroperoxides and carotenoids in AD patients [72].…”

Blood‐based biomarkers for Down syndrome and Alzheimer's disease: A systematic review

“…The Aβ1:42:Aβ1‐40 ratio itself has been shown to be higher among individuals with DS as compared to healthy controls (Iulita et al, ; Matsuoka et al, ). This ratio was also found to be higher among those with DS and AD dementia as compared to those without dementia (Head et al, ; Iulita et al, ; Lee et al, ; Matsuoka et al, ). Among ApoeE4 carriers and non‐carriers, higher concentrations of the Aβ1‐42:Aβ1‐40 ratio were identified among those individuals who have been diagnosed with AD dementia for over 4 years relative to those with less than 4 years since diagnosis (Prasher, Sajith, Mehta, Zigman, & Schupf, ).…”

“…Similar to Aβ1‐42, conflicting results have been shown for plasma Aβ1‐40 with some studies unable to identify a link between DS and AD dementia (Schupf et al, ) while other studies have shown elevated levels (Coppus et al, ; Fortea et al, ; Head et al, ; Iulita et al, ) or decreased levels (Lee et al, ). The link between plasma Aβ1‐40 concentrations among individuals with DS and AD dementia may be less dependent on APOEe4 carrier status as both higher rates have been found among APOEe4 carriers as well as non‐carriers (Head et al, ; Matsuoka et al, ).…”