Skip directly to search Skip directly to A to Z list Skip directly to navigation Skip directly to page options Skip directly to site content

Search PHGKB:

Last Posted: May 16, 2024
spot light Highlights

APOE4 homozygozity represents a distinct genetic form of Alzheimer’s disease

From the abstract: "This study aimed to evaluate the impact of APOE4 homozygosity on Alzheimer’s disease (AD) by examining its clinical, pathological and biomarker changes to see whether APOE4 homozygotes constitute a distinct, genetically determined form of AD. Data from the National Alzheimer’s Coordinating Center and five large cohorts with AD biomarkers were analyzed. The analysis included 3,297 individuals for the pathological study and 10,039 for the clinical study. Findings revealed that almost all APOE4 homozygotes exhibited AD pathology and had significantly higher levels of AD biomarkers from age 55 compared to APOE3 homozygotes. By age 65, nearly all had abnormal amyloid levels in cerebrospinal fluid, and 75% had positive amyloid scans. "

Early dementia diagnosis: blood proteins reveal at-risk people The results of a large-scale screening study could be used to develop blood tests to diagnose diseases such as Alzheimer’s before symptoms take hold.
M Naddaf, Nature, February 13, 2024

From the article: "An analysis of around 1,500 blood proteins has identified biomarkers that can be used to predict the risk of developing dementia up to 15 years before diagnosis. The findings are a step towards a tool that scientists have been in search of for decades: blood tests that can detect Alzheimer’s disease and other forms of dementia at a very early, pre-symptomatic stage. Researchers screened blood samples from more than 50,000 healthy adults in the UK Biobank, 1,417 of whom developed dementia in a 14-year period." They found that high blood levels of four proteins — GFAP, NEFL, GDF15 and LTBP2 — were strongly associated with dementia. "

Assessment of Mendelian and risk factor genes in Alzheimer disease: a prospective nationwide clinical utility study and recommendations for genetic screening
G Nicolas et al, Genetics in Med, January 24, 2024

From the abstract: "We included 700 patients in a prospective study and performed exome sequencing. A panel of 28 Mendelian and 6 risk-factor genes was interpreted and returned to patients. We built a framework for risk variant interpretation and risk gradation and assessed the detection rates among early-onset AD (EOAD, age of onset (AOO) =65 years, n=608) depending on AOO and pedigree structure and late-onset AD (LOAD, 66<AOO<75, n=92).Twenty-one patients carried a LP/P variant in a Mendelian gene (all with EOAD, 3.4%), 20/21 affected APP, PSEN1 or PSEN2. LP/P variant detection rates in EOAD ranged from 1.7% to 11.6% based on AOO and pedigree structure. "

Direct to Consumer Biomarker Testing for Alzheimer Disease—Are We Ready for the Insurance Consequences?
JJ Arias et al, JAMA Neurology, December 18, 2023

From the article: "The promise of DTC testing for AD biomarkers may be lauded by advocates pushing for earlier diagnoses and individuals’ right to know. Early diagnosis of AD through DTC or clinical evaluations could provide benefits, including increased monitoring and preventive care. Additionally, DTC tests could reduce barriers that impede a timely diagnosis (eg, access to dementia specialists). However, DTC tests are not without hazard, particularly given gaps in discriminatory protections for individuals at risk of developing AD with known biomarker status. "

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.