Reversal of Bone Mineral Density Loss Through Lifestyle Changes: A Case Report.

Approximately 10 million individuals in the United States have osteoporosis and 44 million have low bone mineral density which puts them at risk for bone breaks. This presents a large burden on our health care system since about one-quarter of hip fracture patients never regain full function, need nursing care, and, for those over age 50, 24% die within one year. Oral bisphosphonates are often used as first-line therapy for the treatment of osteoporosis; however, patients frequently experience significant side effects.

Diabetes: a tipping point in neurodegenerative diseases.

Diabetes is associated with an increased risk and progression of Alzheimer's (AD) and Parkinson's (PD) diseases. Conversely, diabetes may confer neuroprotection against amyotrophic lateral sclerosis (ALS). It has been posited that perturbations in glucose and insulin regulation, cholesterol metabolism, and mitochondrial bioenergetics defects may underlie the molecular underpinnings of diabetes effects on the brain.

Biological and Clinical Implications of Sex-Specific Differences in Alzheimer's Disease.

Mounting evidence indicates that the female sex is a risk factor for Alzheimer's disease (AD), the most common cause of dementia worldwide. Decades of research suggest that sex-specific differences in genetics, environmental factors, hormones, comorbidities, and brain structure and function may contribute to AD development. However, although significant progress has been made in uncovering specific genetic factors and biological pathways, the precise mechanisms underlying sex-biased differences are not fully characterized.

Diet and lifestyle impact the development and progression of Alzheimer's dementia.

Dementia is a growing public health concern, with an estimated prevalence of 57 million adults worldwide. Alzheimer's disease (AD) accounts for 60-80% of the cases. Clinical trials testing potential drugs and neuroprotective agents have proven futile, and currently approved drugs only provide symptomatic benefits.

Physical activity and lifestyle modifications in the treatment of neurodegenerative diseases.

Neurodegenerative diseases have reached alarming numbers in the past decade. Unfortunately, clinical trials testing potential therapeutics have proven futile. In the absence of disease-modifying therapies, physical activity has emerged as the single most accessible lifestyle modification with the potential to fight off cognitive decline and neurodegeneration.

Co-Expression Network Analysis Identifies Molecular Determinants of Loneliness Associated with Neuropsychiatric and Neurodegenerative Diseases.

Loneliness and social isolation are detrimental to mental health and may lead to cognitive impairment and neurodegeneration. Although several molecular signatures of loneliness have been identified, the molecular mechanisms by which loneliness impacts the brain remain elusive. Here, we performed a bioinformatics approach to untangle the molecular underpinnings associated with loneliness.

Sex-specific transcriptional rewiring in the brain of Alzheimer's disease patients.

Sex-specific differences may contribute to Alzheimer's disease (AD) development. AD is more prevalent in women worldwide, and female sex has been suggested as a disease risk factor. Nevertheless, the molecular mechanisms underlying sex-biased differences in AD remain poorly characterized.

Physical Activity Rewires the Human Brain against Neurodegeneration.

Physical activity may offset cognitive decline and dementia, but the molecular mechanisms by which it promotes neuroprotection remain elusive. In the absence of disease-modifying therapies, understanding the molecular effects of physical activity in the brain may be useful for identifying novel targets for disease management. Here we employed several bioinformatic methods to dissect the molecular underpinnings of physical activity in brain health.

Key Disease Mechanisms Linked to Amyotrophic Lateral Sclerosis in Spinal Cord Motor Neurons.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with no modifying treatments available. The molecular mechanisms underpinning disease pathogenesis are not fully understood. Recent studies have employed co-expression networks to identify key genes, known as "switch genes", responsible for dramatic transcriptional changes in the blood of ALS patients.

Transcriptomic and Network Meta-Analysis of Frontotemporal Dementias.

Frontotemporal lobar degeneration (FTLD), also known as frontotemporal dementia (FTD), results in a progressive decline in executive function, leading to behavioral changes, speech problems, and movement disorders. FTD is the second most common cause of young-onset dementia affecting approximately 5060,000 Americans. FTD exists in familial and sporadic forms, with GRN progranulin and C9orf72 mutations being the most common causes.

Network Analysis Identifies Sex-Specific Gene Expression Changes in Blood of Amyotrophic Lateral Sclerosis Patients.

Understanding the molecular mechanisms underlying the pathogenesis of amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disease, is a major challenge. We used co-expression networks implemented by the SWitch Miner software to identify switch genes associated with drastic transcriptomic changes in the blood of ALS patients. Functional analyses revealed that switch genes were enriched in pathways related to the cell cycle, hepatitis C, and small cell lung cancer.

Key Disease Mechanisms Linked to Alzheimer's Disease in the Entorhinal Cortex.

Alzheimer's disease (AD) is a chronic, neurodegenerative brain disorder affecting millions of Americans that is expected to increase in incidence with the expanding aging population. Symptomatic AD patients show cognitive decline and often develop neuropsychiatric symptoms due to the accumulation of insoluble proteins that produce plaques and tangles seen in the brain at autopsy. Unexpectedly, some clinically normal individuals also show AD pathology in the brain at autopsy (asymptomatic AD, AsymAD).

The Impact of Disease Comorbidities in Alzheimer's Disease.

A wide range of comorbid diseases is associated with Alzheimer's disease (AD), the most common neurodegenerative disease worldwide. Evidence from clinical and molecular studies suggest that chronic diseases, including diabetes, cardiovascular disease, depression, and inflammatory bowel disease, may be associated with an increased risk of AD in different populations. Disruption in several shared biological pathways has been proposed as the underlying mechanism for the association between AD and these comorbidities.

A Comparison of Gene Expression Changes in the Blood of Individuals Consuming Diets Supplemented with Olives, Nuts or Long-Chain Omega-3 Fatty Acids.

Background: The Mediterranean diet, which is rich in olive oil, nuts, and fish, is considered healthy and may reduce the risk of chronic diseases.

Methods: Here, we compared the transcriptome from the blood of subjects with diets supplemented with olives, nuts, or long-chain omega-3 fatty acids and identified the genes differentially expressed. The dietary genes obtained were subjected to network analysis to determine the main pathways, as well as the transcription factors and microRNA interaction network to elucidate their regulation.

Bioinformatic Analysis Reveals Phosphodiesterase 4D-Interacting Protein as a Key Frontal Cortex Dementia Switch Gene.

The mechanisms that initiate dementia are poorly understood and there are currently no treatments that can slow their progression. The identification of key genes and molecular pathways that may trigger dementia should help reveal potential therapeutic reagents. In this study, SWItch Miner software was used to identify phosphodiesterase 4D-interacting protein as a key factor that may lead to the development of Alzheimer's disease, vascular dementia, and frontotemporal dementia.

Transcriptomic and Network Analysis Identifies Shared and Unique Pathways across Dementia Spectrum Disorders.

Background: Dementia is a growing public health concern with an estimated prevalence of 50 million people worldwide. Alzheimer's disease (AD) and vascular and frontotemporal dementias (VaD, FTD), share many clinical, genetical, and pathological features making the diagnosis difficult.

Methods: In this study, we compared the transcriptome from the frontal cortex of patients with AD, VaD, and FTD to identify dysregulated pathways.

Transcriptomic and Network Analysis Highlight the Association of Diabetes at Different Stages of Alzheimer's Disease.

Alzheimer's disease (AD) and type 2 diabetes (T2D) are among the most prevalent chronic diseases affecting the aging population. Extensive research evidence indicates that T2D is a well-established risk factor for AD; however, the molecular mechanisms underlying this association have not been fully elucidated. Furthermore, how T2D may contribute to the progression of AD is a subject of extensive investigation.

Meta-Analysis of Gene Expression Changes in the Blood of Patients with Mild Cognitive Impairment and Alzheimer's Disease Dementia.

Background: Dementia is a major public health concern affecting approximately 47 million people worldwide. Mild cognitive impairment (MCI) is one form of dementia that affects an individual's memory with or without affecting their daily life. Alzheimer's disease dementia (ADD) is a more severe form of dementia that usually affects elderly individuals.

Computational identification of key genes that may regulate gene expression reprogramming in Alzheimer's patients.

The dementia epidemic is likely to expand worldwide as the aging population continues to grow. A better understanding of the molecular mechanisms that lead to dementia is expected to reveal potentially modifiable risk factors that could contribute to the development of prevention strategies. Alzheimer's disease is the most prevalent form of dementia.

PTPRC Expression in Blood is Downregulated in Parkinson's and Progressive Supranuclear Palsy Disorders.

Background: Parkinson's disease (PD) shares pathological and clinical features with progressive supranuclear palsy (PSP) patients making the diagnosis challenging. Distinguishing PD from PSP is crucial given differences in disease course, treatment and clinical management.

Objective: Although some progress has been made in the discovery of biomarkers for PD and PSP, there is an urgent need to identify additional biomarkers capable of distinguishing between these diseases.

Evaluation of RNA Blood Biomarkers in the Parkinson's Disease Biomarkers Program.

There is a high misdiagnosis rate between Parkinson's disease (PD) and atypical parkinsonian disorders (APD), such as progressive supranuclear palsy (PSP), the second most common parkinsonian syndrome. In our earlier studies, we identified and replicated RNA blood biomarkers in several independent cohorts, however, replication in a cohort that includes PSP patients has not yet been performed. To this end, we evaluated the diagnostic potential of nine previously identified RNA biomarkers using quantitative PCR assays in 138 blood samples at baseline from PD, PSP and healthy controls (HCs) nested in the PD Biomarkers Program.

Biological and Clinical Implications of Comorbidities in Parkinson's Disease.

A wide spectrum of comorbidities has been associated with Parkinson's disease (PD), a progressive neurodegenerative disease that affects more than seven million people worldwide. Emerging evidence indicates that chronic diseases including diabetes, depression, anemia and cancer may be implicated in the pathogenesis and progression of PD. Recent epidemiological studies suggest that some of these comorbidities may increase the risk of PD and precede the onset of motor symptoms.

Evaluation of RNA Blood Biomarkers in Individuals at Risk of Parkinson's Disease.

Background: Substantial progress has been made in the discovery of blood biomarkers for Parkinson's disease (PD), a progressive neurodegenerative disease that affects more than 4 million worldwide. Olfactory dysfunction and dopamine deficits usually precede motor symptoms years before the onset of PD. A readily accessible biomarker useful for identifying patients at risk of PD is expected to accelerate clinical trials.

Parkinson's disease biomarkers: perspective from the NINDS Parkinson's Disease Biomarkers Program.

Biomarkers for Parkinson's disease (PD) diagnosis, prognostication and clinical trial cohort selection are an urgent need. While many promising markers have been discovered through the National Institute of Neurological Disorders and Stroke Parkinson's Disease Biomarker Program (PDBP) and other mechanisms, no single PD marker or set of markers are ready for clinical use. Here we discuss the current state of biomarker discovery for platforms relevant to PDBP.

Dissecting the Molecular Mechanisms of Neurodegenerative Diseases through Network Biology.

Neurodegenerative diseases are rarely caused by a mutation in a single gene but rather influenced by a combination of genetic, epigenetic and environmental factors. Emerging high-throughput technologies such as RNA sequencing have been instrumental in deciphering the molecular landscape of neurodegenerative diseases, however, the interpretation of such large amounts of data remains a challenge. Network biology has become a powerful platform to integrate multiple omics data to comprehensively explore the molecular networks in the context of health and disease.