Country Level Incidence of Alzheimer Disease and Related Dementias is Associated with Increased Omega6 PUFA Consumption.

INTRODUCTION: Clinical and genetic studies have implicated lipid dysfunction in Alzheimer Disease (AD) pathogenesis. However, lipid consumption at the individual-level does not vary greatly within most cohorts, and multiple lipids are rarely measured in any one study. METHODS: Mean country-level lipid intakes were compared to Age-Standardized Alzheimer-Disease-Incidence-Rates(ASAIR) in 183 countries across all inhabited continents. Penalized spline regression and multivariable-adjusted linear regression, including a lag between intake and incidence, were used to assess the relationships between five lipid intakes and ASAIR. Validation was conducted using longitudinal within-country changes between 1990 and 2019. RESULTS: Omega6 Polyunsaturated-Fatty-Acid(PUFA) intake exhibited a positive linear relationship with ASAIR(multivariable-adjusted model: ß=2.44; 95%CI: 1.70, 3.19; p=1.38×10-9). ASAIR also increased with saturated-fat, trans-fat, and dietary-cholesterol up to a threshold. The association between Omega6-PUFA and ASAIR was confirmed using longitudinal intake changes. DISCUSSION: Decreasing Omega6-PUFA consumption on the country-level may have substantial benefits in reducing the country-level burden of AD.

Fetal High-Risk APOL1 Genotype Increases Risk for Small for Gestational Age in Term Infants Affected by Preeclampsia.

BACKGROUND: Hypertensive disorders of pregnancy cause fetal growth restriction and increased maternal morbidity and mortality, especially in women of African ancestry. Recently, preeclampsia risk was associated with polymorphisms in the apolipoprotein L1 (APOL1) gene in women of African ancestry. OBJECTIVES: We assessed APOL1 genotype effects on pregnancies with and without preeclampsia. METHOD: We conducted an unmatched case-control study of 1,358 mother-infant pairs from two independent cohorts of black women. RESULTS: Term preeclampsia cases with high-risk APOL1 genotypes were more likely to be small for gestational age compared to APOL1 low-risk term cases (odds ratio [OR] 2.8) and APOL1 high-risk controls (OR 5.5). Among preterm pregnancies, fetal APOL1 genotype was associated with preeclampsia. CONCLUSIONS: Fetal APOL1 genotype was associated with preeclampsia in preterm infants and with altered fetal growth in term infants. This may indicate APOL1 genotype impacts a spectrum of pregnancy complications mediated by a common pathophysiological event of placental insufficiency.

An Atoh1 CRE Knock-In Mouse Labels Motor Neurons Involved in Fine Motor Control.

Motor neurons (MNs) innervating the digit muscles of the intrinsic hand (IH) and intrinsic foot (IF) control fine motor movements. The ability to reproducibly label specifically IH and IF MNs in mice would be a beneficial tool for studies focused on fine motor control. To this end, we find that a CRE knock-in mouse line of Atoh1, a developmentally expressed basic helix-loop-helix (bHLH) transcription factor, reliably expresses CRE-dependent reporter genes in ∼60% of the IH and IF MNs. We determine that CRE-dependent expression in IH and IF MNs is ectopic because an Atoh1 mouse line driving FLPo recombinase does not label these MNs although other Atoh1-lineage neurons in the intermediate spinal cord are reliably identified. Furthermore, the CRE-dependent reporter expression is enriched in the IH and IF MN pools with much sparser labeling of other limb-innervating MN pools such as the tibialis anterior (TA), gastrocnemius (GS), quadricep (Q), and adductor (Ad). Lastly, we find that ectopic reporter expression begins postnatally and labels a mixture of α and γ-MNs. Altogether, the Atoh1 CRE knock-in mouse strain might be a useful tool to explore the function and connectivity of MNs involved in fine motor control when combined with other genetic or viral strategies that can restrict labeling specifically to the IH and IF MNs. Accordingly, we provide an example of sparse labeling of IH and IF MNs using an intersectional genetic approach.