Systematic review and evidence gap mapping of Alzheimer's disease biomarker studies in those with intellectual and developmental disability.

There are a relatively small number of investigations into brain aging in those with intellectual and developmental disability (I/DD). This project seeks to (1) characterize the internationally available multi-omics Alzheimer's disease (AD) biomarker studies including those with I/DD, and (2) discuss future research directions. PubMed, Web of Science, and Scopus were searched under the following criteria: cross-sectional or longitudinal AD-omics studies on adults (18 +) with I/DD. 532 studies were identified, 186 studies were evaluated for full-text, 79 studies were excluded, and 117 studies were extracted. Most biological specimens were analyzed in blood, plasma, or serum. Metabolomics, hormonomics, and transcriptomics were most understudied. Sex differences were investigated in nine studies. Two studies included participants with non-Down syndrome neurodevelopmental disorders. European-based city populations were primarily represented across studies. Future studies including a broader range of I/DD presentations, and considering sex differences, comorbidities, and novel biomarkers beta synuclein are interesting future directions. Highlights: Small sample sizes, cross-sectional designs, and few prospective and retrospective studies highlight the need for more rigorous research design.A focus on European-based city populations and Down syndrome (DS) clinical groups prompts the need for inclusive, community-based recruitment methods across broader clinical and ethnic groups.The vesicle-associated membrane protein 2 (VAMP2) shows promise for early detection of synaptic degeneration, potentially across I/DD groups, showing correlations with CSF biomarkers of Alzheimer's disease, axonal injury, and cognitive performance in DS.