Differential CSF biomarkers in autosomal dominant AD and Down syndrome

In a cross-sectional study of Alzheimer’s disease (AD) in people with Down syndrome, study researchers observed significant differences in levels of amyloid b (Ab) and chitinase 3-line protein 1 (YKL-40) compared to patients with AD . These results were published in the Lancet Neurology.

As part of the Alzheimer’s Biomarker Consortium-Down Syndrome (ABC-DS) study, patients with Down syndrome and autosomal dominant AD mutations were recruited between 2015 and 2018. The Dominantly Inherited Alzheimer Network (DIAN) study, which included people who Were carriers of AD mutations, and their siblings who were not carriers.

Participants with Down syndrome (n = 41) included 26 men and 15 women, and participants in the DIAN study (n = 300) included 137 men and 163 women who were dominant mutant carriers (n = 192) and theirs Siblings without a carrier (n = 108.). ).

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The 3 cohorts differed significantly with regard to age, cognitive status and all CSF biomarkers (all P <0.001).

Compared to the siblings without carrier, the Down syndrome cohort differed significantly for the CSF biomarkers total tau, p-tau181, Ab1-42: Ab1-40 ratio and visinin-like protein 1 (VILIP-1; all P <0.008). Compared to the AD carriers, the Down syndrome cohort differed significantly for Ab1-42 (P <0.0008). Compared with both groups, the Down syndrome individuals differed significantly for Ab1-40, total tau: Ab1-42, p-tau181: Ab1-42 and YKL-40.

Dementia was symptomatic in 34% of the Down syndrome and 43% of the AD mutation carriers. Ab1-40 levels differed significantly among symptomatic individuals with Down syndrome (P = .040). Among all symptomatic subjects, Ab1-42 was significantly lower (P £ 0.001) and YKL-40 was significantly higher (P £ 0.01).

The study researchers modeled the course of AD as a function of age. The age-related biomarker patterns were similar in both the Down syndrome and the mutation carrier cohort; even fewer markers in the Down syndrome cohort were significantly different from the non-carriers. However, those with Down syndrome had higher Ab1-40 and larger YKL-40 slopes than either cohort, and they did not differ from the non-carriers in the slope of total tau or tau: Ab1-42.

This study was limited by the power due to the small number of samples from individuals with Down syndrome.

These data showed that CSF biomarker patterns in individuals with Down syndrome who were carriers of AD mutations exhibited many similar patterns to individuals with AD, except that Down syndrome was associated with different Ab and YKL-40 trajectories .

Disclosure: Several authors stated links to the pharmaceutical industry. For a full list of the details, see the original article.


Fagan AM, Henson RL, Li Y, et al. Comparison of CSF biomarkers in Down syndrome and autosomal dominant Alzheimer’s disease: a cross-sectional study. Lancet Neurol. 2021; 20 (8): 615-626. doi: 10.1016 / S1474-4422 (21) 00139-3

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