Basic Science and Pathogenesis.

Background: APOE*4 is the strongest genetic risk for late-onset Alzheimer's disease (AD), but other genetic loci may counter its detrimental effect, providing therapeutic avenues. Expanding beyond non-Hispanic White subjects, we sought to additionally leverage genetic data from non-Hispanic and Hispanic subjects of admixed African ancestry to perform trans-ancestry APOE*4-stratified GWAS, anticipating that allele frequency differences across populations would boost power for gene discovery.

Method: Participants were ages 60+, of European (EU; ≥75%) or admixed African (AFR; ≥25%) ancestry, and diagnosed as cases or controls.

Basic Science and Pathogenesis.

Background: Several studies have indicated sex-specific genetic risk for Alzheimer's disease (AD), but these were centered on non-Hispanic White individuals of European ancestry. We sought to identify sex-specific genetic variants for AD in non-Hispanic and Hispanic subjects of admixed African ancestry.

Method: Participants were ages 60+, of African ancestry (≥25%), and diagnosed as cases or controls.

Mitochondrial Functioning: Front and Center in Defining Psychosomatic Mechanisms of Allostasis in Health and Disease.

There is increased awareness among basic and clinical scientists that psychological and social stress can have detrimental effects on physical, cognitive, and mental health. Data have been published indicating that social, economic, psychological, and physical environmental stress can influence behavior that has biological and physiological consequences-yet there are major gaps in understanding the physiological and cellular processes that drive increased morbidity and mortality. The potential role of mitochondria has been highlighted in psychosomatic medicine, as their functionality in various biological and physiological processes has earned recognition.

Surgical Primary Tumor Resection Reduces Accumulation of CD11b Myeloid Cells in the Lungs Augmenting the Efficacy of an Intranasal Cancer Vaccination against Secondary Lung Metastasis.

A hallmark of effective cancer treatment is the prevention of tumor reoccurrence and metastasis to distal organs, which are responsible for most cancer deaths. However, primary tumor resection is expected to be curative as most solid tumors have been shown both experimentally and clinically to accelerate metastasis to distal organs including the lungs. In this study, we evaluated the efficacy of our engineered nasal nano-vaccine (CpG-NP-Tag) in reducing accelerated lung metastasis resulting from primary tumor resection.

Blood-Based mtDNA Quantification Indicates Population-Specific Differences Associated with Alzheimer's Disease-Related Risk.

Background: Age is known to be the biggest risk factor for Alzheimer's disease (AD), and Mexican Americans (MAs), who are one of the fastest-aging populations in the United States, are at a uniquely elevated risk. Mitochondrial stress and dysfunction are key players in the progression of AD and are also known to be impacted by lifestyle and environmental exposures/stressors.

Objective: This study aimed to identify population-specific differences in indicators of mitochondrial stress and dysfunction associated with AD risk that are detectable in the blood.

Integrative blood-based characterization of oxidative mitochondrial DNA damage variants implicates Mexican American's metabolic risk for developing Alzheimer's disease.

Alzheimer's Disease (AD) continues to be a leading cause of death in the US. As the US aging population (ages 65 +) expands, the impact will disproportionately affect vulnerable populations, e.g.

Maternal and fetal mitochondrial gene dysregulation in hypertensive disorders of pregnancy.

Mitochondrial dysfunction has been implicated in pregnancy-induced hypertension (PIH). The role of mitochondrial gene dysregulation in PIH, and consequences for maternal-fetal interactions, remain elusive. Here, we investigated mitochondrial gene expression and dysregulation in maternal and placental tissues from pregnancies with and without PIH; further, we measured circulating mitochondrial DNA (mtDNA) mutational load, an index of mtDNA integrity.

Integrative Blood-Based Characterization of Oxidative Mitochondrial DNA Damage Variants Implicates Mexican Americans' Metabolic Risk for Developing Alzheimer's Disease.

Alzheimer's Disease (AD) continues to be a leading cause of death in the US. As the US aging population (ages 65+) expands, the impact will disproportionately affect vulnerable populations, e.g.

Nasal Tumor Vaccination Protects against Lung Tumor Development by Induction of Resident Effector and Memory Anti-Tumor Immune Responses.

Lung metastasis is a leading cause of cancer-related deaths. Here, we show that intranasal delivery of our engineered CpG-coated tumor antigen (Tag)-encapsulated nanoparticles (NPs)-nasal nano-vaccine-significantly reduced lung colonization by intravenous challenge of an extra-pulmonary tumor. Protection against tumor-cell lung colonization was linked to the induction of localized mucosal-associated effector and resident memory T cells as well as increased bronchiolar alveolar lavage-fluid IgA and serum IgG antibody responses.

Mitochondrial DNA oxidative mutations are elevated in Mexican American women potentially implicating Alzheimer's disease.

Mexican Americans (MAs) are the fastest-growing Hispanic population segment in the US; as this population increases in age, so will the societal burden of age-related diseases such as Alzheimer's disease (AD). Mitochondrial DNA (mtDNA) damage may be implicated in MA AD risk since metabolic comorbidities are more prevalent in this group. Oxidative damage to guanosine (8oxoG) is one of the most prevalent DNA lesions and a putative indicator of mitochondrial dysfunction.

HIV-1 infection renders brain vascular pericytes susceptible to the extracellular glutamate.

Reduced pericytes' coverage of endothelium in the brain is one of the structural changes leading to breach of the blood-brain barrier during HIV infection. We previously showed in central memory T (T) cells that HIV latency increases cellular susceptibility to DNA damage. In this study, we investigated susceptibility of primary brain pericytes infected with HIV-1 to DNA damage in response to glutamate and TNF-α, both known to induce neuronal death during chronic inflammatory conditions.