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Last Posted: Dec 04, 2022
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A Promising Trial Targets a Genetic Risk for Alzheimer’s
G Kolata, NY Times, December 2, 2022

Preliminary results offer hope that gene therapy can protect people with a version of the brain disease driven by a particular gene variant. Participants in the study are among the approximately 2 percent of people who have inherited a pair of copies of a gene, APOE4, which markedly increases their risk of Alzheimer’s.

Differential roles of Aβ42/40, p-tau231 and p-tau217 for Alzheimer's trial selection and disease monitoring.
Ashton Nicholas J et al. Nature medicine 2022 12

In the BioFINDER-1 cohort, plasma phosphorylated (p)-tau231 and amyloid-ß42/40 ratio were more changed at lower thresholds of amyloid pathology. Longitudinally, however, only p-tau217 demonstrated marked amyloid-dependent changes over 4–6?years in both preclinical and symptomatic stages of the disease. The selective longitudinal increase of p-tau217 and its associations with cognitive decline and atrophy was confirmed in an independent cohort (Wisconsin Registry for Alzheimer’s Prevention). These findings support the differential association of plasma biomarkers with disease development and strongly highlight p-tau217 as a surrogate marker of disease progression.

Cost-effectiveness of a gene sequencing test for Alzheimer's disease in Ontario.
Iragorri Nicolas et al. Journal of community genetics 2022 11

ONDRISeq saved $54 per patient relative to OOC testing and led to a small QALY gain in the base case (0.0014 per patient). Results were most sensitive to testing costs, uptake rates, and treatment efficacy. ONDRISeq represented better value for money relative to OOC testing throughout 75% of 10,000 probabilistic iterations. Using ONDRISeq is expected to provide health system cost savings. Switching to ONDRISeq for AD genetic testing would be dependent on the ability to accommodate the expected testing volumes.

Exome sequencing identifies rare damaging variants in ATP8B4 and ABCA1 as risk factors for Alzheimer's disease.
Holstege Henne et al. Nature genetics 2022 11

We compared the gene-based burden of rare damaging variants in exome sequencing data from 32,558 individuals—16,036 AD cases and 16,522 controls. Next to variants in TREM2, SORL1 and ABCA7, we observed a significant association of rare, predicted damaging variants in ATP8B4 and ABCA1 with AD risk, and a suggestive signal in ADAM10. Additionally, the rare-variant burden in RIN3, CLU, ZCWPW1 and ACE highlighted these genes as potential drivers of respective AD-genome-wide association study loci.

Disclaimer: Articles listed in the Public Health Genomics and Precision Health Knowledge Base are selected by the CDC Office of Public Health Genomics to provide current awareness of the literature and news. Inclusion in the update does not necessarily represent the views of the Centers for Disease Control and Prevention nor does it imply endorsement of the article's methods or findings. CDC and DHHS assume no responsibility for the factual accuracy of the items presented. The selection, omission, or content of items does not imply any endorsement or other position taken by CDC or DHHS. Opinion, findings and conclusions expressed by the original authors of items included in the update, or persons quoted therein, are strictly their own and are in no way meant to represent the opinion or views of CDC or DHHS. References to publications, news sources, and non-CDC Websites are provided solely for informational purposes and do not imply endorsement by CDC or DHHS.