Response to Fuson, Clements, and Sarama Commentary on Litkowski, Duncan, Logan, and Purpura (2020)

In response to Fuson et al.’s commentary on Litkowski et al. (2020), we clarify and expand on three areas: (1) the need for prekindergarten standards, (2) the value in developmental survey work, and (3) the importance of understanding curriculum translation and uptake. Specifically, we note that standards need to be appropriate for grade-level and it is time for more aligned prekindergarten standards. Developmental survey work is critical for ensuring that standards and expectations are accurate and adjusted to meet current needs and can be used address equity issues in instruction. Furthermore, we agree that intervention and curriculum work are needed, but there should be explicit emphasis on enhancing uptake and use of high-quality instruction. Ultimately, we need a system of assessment and instruction that is continually updated and improved, that integrates and modifies new evidence over time to ensure that we are striving for—and attaining—the best results for young children

New insights into the genetic etiology of Alzheimer’s disease and related dementias

Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

New insights into the genetic etiology of Alzheimer’s disease and related dementias

Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele