. 2021 Aug 17;10(16):3639. doi: 10.3390/jcm10163639

Table 1.

AD core blood biomarkers studied in DS and DS-dementia. Each biomarker is categorized with (A), (T) or (N) depending on the pathology they reflect within the A/T/N system.

Biomarker	DS Compared with Healthy Controls	DS-AD Compared with Cognitively Stable DS	Diagnostic Application	Future Challenges
Aβ (A)	Increased levels of Aβ₄₀ and Aβ₄₂. Contradictory results for Aβ₄₂/Aβ₄₀ ratio and for association between Aβ₄₂ and age.	Higher plasma Aβ₄₀ and lower Aβ₄₂/Aβ₄₀ ratio in demented DS. No association between Aβ₄₂ and dementia status.	Low diagnostic performance. Overlap between groups.	Quantification by sensitive IP-MS. Analysis of other Aβ species other than Aβ₄₀ and Aβ₄₂ (Aβ₃₇, Aβ₃₈, Aβ₄₁)
p-tau181 (T)	Increased from early 30s. P-tau396 also found increased in neuronal exosomes.	Increased levels in both prodromal AD and AD dementia. Earlier increases in APOE ε4 allele carriers.	High diagnostic accuracy to differentiate AD dementia, low for prodromal AD.	Study of other tau phosphorylations: p-tau205, p-tau217, p-tau231.
T-tau (N)	Increased. Positive correlation between age and plasma t-tau in DS.	Significantly higher levels in DS-AD but weak increase in prodromal AD.	Low diagnostic performance. Overlap between groups.	New sensitive assays that target CNS specific tau.
NfL (N)	Increased. Positive correlation between age and plasma NfL.	Increased levels in both prodromal AD and AD dementia.	High diagnostic performance for both prodromal AD and AD dementia.	Use as diagnostic tool in clinical routine. Combination with cognitive assessment.