*Article* **Acute Regression in Down Syndrome**

**Benjamin Handen 1,\*, Isabel Clare <sup>2</sup> , Charles Laymon <sup>1</sup> , Melissa Petersen <sup>3</sup> , Shahid Zaman <sup>2</sup> , Sid O'Bryant <sup>3</sup> , Davneet Minhas <sup>1</sup> , Dana Tudorascu <sup>1</sup> , Stephanie Brown <sup>2</sup> , and Bradley Christian <sup>4</sup> on behalf of the Alzheimer's Biomarker Consortium-Down Syndrome (ABC-DS)**


**Abstract:** Background: Acute regression has been reported in some individuals with Down syndrome (DS), typically occurring between the teenage years and mid to late 20s. Characterized by sudden, and often unexplained, reductions in language skills, functional living skills and reduced psychomotor activity, some individuals have been incorrectly diagnosed with Alzheimer's disease (AD). Methods: This paper compares five individuals with DS who previously experienced acute regression with a matched group of 15 unaffected individuals with DS using a set of AD biomarkers. Results: While the sample was too small to conduct statistical analyses, findings suggest there are possible meaningful differences between the groups on proteomics biomarkers (e.g., NfL, total tau). Hippocampal, caudate and putamen volumes were slightly larger in the regression group, the opposite of what was hypothesized. A slightly lower amyloid load was found on the PET scans for the regression group, but no differences were noted on tau PET. Conclusions: Some proteomics biomarker findings suggest that individuals with DS who experience acute regression may be at increased risk for AD at an earlier age in comparison to unaffected adults with DS. However, due to the age of the group (mean 38 years), it may be too early to observe meaningful group differences on image-based biomarkers.

**Keywords:** down syndrome; regression; Alzheimer's disease; biomarkers
