DNA methylation age from peripheral blood predicts progression to Alzheimer's disease, white matter disease burden, and cortical atrophy.

Cross-sectional studies suggest a limited relationship between accelerated epigenetic aging derived from epigenetic clocks, and Alzheimer's disease (AD) pathophysiology or risk. However, most prior analyses have not utilized longitudinal analyses or whole-brain neuroimaging biomarkers of AD. Herein, we employed longitudinal modeling and structural neuroimaging analyses to test the hypothesis that accelerated epigenetic aging would predict AD progression.

Expansion of highly interferon-responsive T cells in early-onset Alzheimer's disease.

Introduction: Altered immune signatures are emerging as a central theme in neurodegenerative disease, yet little is known about immune responses in early-onset Alzheimer's disease (EOAD).

Methods: We examined single-cell RNA-sequencing (scRNA-seq) data from peripheral blood mononuclear cells (PBMCs) and droplet digital polymerase chain reaction (ddPCR) data from CD4 T cells from participants with EOAD and clinically normal controls.

Results: We analyzed PBMCs from 16 individuals by scRNA-seq and discovered increased interferon signaling-associated gene (ISAG) expression and striking expansion of antiviral-like ISAG T cells in EOAD.

gene networks in the human brain correlate with cortical thickness in C9-FTD and implicate vulnerable cell types.

Introduction: A hexanucleotide repeat expansion (HRE) intronic to chromosome 9 open reading frame 72 () is recognized as the most common genetic cause of amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and ALS-FTD. Identifying genes that show similar regional co-expression patterns to may help identify novel gene targets and biological mechanisms that mediate selective vulnerability to ALS and FTD pathogenesis.

Methods: We leveraged mRNA expression data in healthy brain from the Allen Human Brain Atlas to evaluate co-expression patterns.

Expansion of highly interferon-responsive T cells in early-onset Alzheimer's disease.

Introduction: Altered immune signatures are emerging as a central theme in neurodegenerative disease, yet little is known about immune responses in early-onset Alzheimer's disease (EOAD).

Methods: We examined single-cell RNA-sequencing (scRNA-seq) data from peripheral blood mononuclear cells (PBMCs) and droplet digital (dd)PCR data from CD4 T cells from participants with EOAD and clinically normal controls.

Results: We analyzed ~182,000 PBMCs by scRNA-seq and discovered increased interferon signaling-associated gene (ISAG) expression and striking expansion of antiviral-like ISAG T cells in EOAD.

gene networks in the human brain correlate with cortical thickness in C9-FTD and implicate vulnerable cell types.

Introduction: A hexanucleotide repeat expansion (HRE) intronic to chromosome 9 open reading frame 72 () is recognized as the most common genetic cause of amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and ALS-FTD. Identifying genes that show similar regional co-expression patterns to may help identify novel gene targets and biological mechanisms that mediate selective vulnerability to ALS and FTD pathogenesis.

Methods: We leveraged mRNA expression data in healthy brain from the Allen Human Brain Atlas to evaluate co-expression patterns.

Single-cell RNA-seq reveals alterations in peripheral CX3CR1 and nonclassical monocytes in familial tauopathy.

Background: Emerging evidence from mouse models is beginning to elucidate the brain's immune response to tau pathology, but little is known about the nature of this response in humans. In addition, it remains unclear to what extent tau pathology and the local inflammatory response within the brain influence the broader immune system.

Methods: To address these questions, we performed single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) from carriers of pathogenic variants in MAPT, the gene encoding tau (n = 8), and healthy non-carrier controls (n = 8).

Association of Optic Nerve Head and Macular Optical Coherence Tomography Measures With Glaucoma-Related Disability.

Prcis: Optical coherence tomography (OCT) estimated retinal nerve fiber layer (RNFL) thickness associated with glaucoma-related disability independent of the visual field (VF) damage and thus may provide additional patient-relevant disability information beyond what is captured by standard VF testing.

Purpose: To examine whether OCT metrics [peripapillary RNFL thickness and macular ganglion cell/inner plexiform layer (GCIPL) thickness] are associated with quality of life (QoL) measures and additional disability metrics, and whether these associations are independent of VF damage.

Methods: In this cross-sectional study, 156 patients with glaucoma or suspected glaucoma received VF testing and OCT scans to measure RNFL and GCIPL thickness.

Radiogenomics of Expansion Carriers Reveals Global Transposable Element Derepression and Enables Prediction of Thalamic Atrophy and Clinical Impairment.

Hexanucleotide repeat expansion (HRE) within is the most common genetic cause of frontotemporal dementia (FTD). Thalamic atrophy occurs in both sporadic and familial FTD but is thought to distinctly affect HRE carriers. Separately, emerging evidence suggests widespread derepression of transposable elements (TEs) in the brain in several neurodegenerative diseases, including HRE-mediated FTD (C9-FTD).

Case Report: Novel Variant in a Patient With Behavioral Variant Frontotemporal Dementia Syndrome With Prodromal Repetitive Scratching Behavior.

-related leukoencephalopathy is an autosomal dominant neurodegenerative disease caused by mutations in the tyrosine kinase domain of the colony stimulating factor 1 receptor (CSF1R). Several studies have found that hematogenic stem cell transplantation is an effective disease modifying therapy however the literature regarding prodromal and early symptoms -related leukoencephalopathy is limited. We describe a 63-year-old patient with 4 years of repetitive scratching and skin picking behavior followed by 10 years of progressive behavioral, cognitive, and motor decline in a pattern suggesting behavioral variant of frontotemporal dementia.

Dissecting the clinical heterogeneity of early-onset Alzheimer's disease.

Early-onset Alzheimer's disease (EOAD) is a rare but particularly devastating form of AD. Though notable for its high degree of clinical heterogeneity, EOAD is defined by the same neuropathological hallmarks underlying the more common, late-onset form of AD. In this review, we describe the various clinical syndromes associated with EOAD, including the typical amnestic phenotype as well as atypical variants affecting visuospatial, language, executive, behavioral, and motor functions.

The Role of Microglia in Inherited White-Matter Disorders and Connections to Frontotemporal Dementia.

Microglia play a critical but poorly understood role in promoting white-matter homeostasis. In this review, we leverage advances in human genetics and mouse models of leukodystrophies to delineate our current knowledge and identify outstanding questions regarding the impact of microglia on central nervous system white matter. We first focus on the role of pathogenic mutations in genes, such as , and that cause leukodystrophies in which the primary deficit is thought to originate in microglia.

Diagnostic and interventional magnetic resonance neurography diagnosis of brachytherapy seed-mediated pudendal nerve injury: a case report.

Injury to the pudendal nerve in men presents with pain, paresthesia, or numbness of the perineum, and/or scrotum, and/or penis. There is evidence implicating the brachytherapy seeds used to treat prostate cancer as source of pudendal nerve injury. Compared to surgical prostatectomy, brachytherapy has the advantage of being less invasive, but seeds may not only lead to well-established complications such as urinary, bowel, and erectile dysfunction, but also injury to the sensory branches of the pudendal nerve.

Needle Heating During Interventional Magnetic Resonance Imaging at 1.5- and 3.0-T Field Strengths.

Objectives: The aim of this study was to test the hypothesis that clinically used magnetic resonance (MR)-conditional needles of varying lengths, orientations, locations, and pulse sequences can result in excessive heating during MR imaging (MRI)-guided interventions that can be minimized to physiological ranges with proper selection of the needle length, needle position, and modification of pulse sequence parameters.

Materials And Methods: We simulated a clinical interventional MRI setting with 2 standard American Society for Testing and Materials F2182-11A phantoms and measured temperatures with fiber optic sensors. Temperature profiles were monitored for commercial 10, 15 and 20 cm MR-conditional cobalt-chromium needles in clinically relevant perpendicular, 45-degree oblique, and parallel orientations relative to the static magnetic field (B0) and center, right off-center, and left off-center needle tip locations in the z = 0 plane.

Non-coding and Loss-of-Function Coding Variants in TET2 are Associated with Multiple Neurodegenerative Diseases.

We conducted genome sequencing to search for rare variation contributing to early-onset Alzheimer's disease (EOAD) and frontotemporal dementia (FTD). Discovery analysis was conducted on 435 cases and 671 controls of European ancestry. Burden testing for rare variation associated with disease was conducted using filters based on variant rarity (less than one in 10,000 or private), computational prediction of deleteriousness (CADD) (10 or 15 thresholds), and molecular function (protein loss-of-function [LoF] only, coding alteration only, or coding plus non-coding variants in experimentally predicted regulatory regions).

Exploring Patient Motivations and Impact of Asian Blepharoplasty.

To date, patient motivations for Asian blepharoplasty and the surgery's impact on quality of life have not been quantified. Here, we employed structured interviews and a web-based survey to better characterize patient motivations for Asian blepharoplasty and the impact of Asian blepharoplasty on self-reported domains of happiness, self-esteem, attractiveness, social life, and professional life. Structured interviews were conducted to inform a web-based survey regarding Asian blepharoplasty.

The Radiogenomics of Late-onset Alzheimer Disease.

Radiogenomics, defined as the integrated analysis of radiologic imaging and genetic data, is a well-established tool shown to augment neuroimaging in the clinical diagnosis, prognostication, and scientific study of late-onset Alzheimer disease (LOAD). Early work using candidate single nucleotide polymorphisms (SNPs) identified genetic variation in APOE, BIN1, CLU, and CR1 as key modifiers of brain structure and function using magnetic resonance imaging (MRI). More recently, polygenic risk scores used in conjunction with MRI and positron emission tomography have shown great promise as a risk-stratification tool for clinical trials and care-management decisions.

Recent advances in the genetics of frontotemporal dementia.

Purpose Of Review: In this review we highlight recent advances in the human genetics of frontotemporal dementia (FTD). In addition to providing a broad survey of genes implicated in FTD in the last several years, we also discuss variation in genes implicated in both hereditary leukodystrophies and risk for FTD (e.g.

Evidence-Based Criteria for Determining Peripapillary OCT Reliability.

Purpose: To assess the impact of OCT signal strength (SS) and artifact on retinal nerve fiber layer (RNFL) measurement reliability and to understand whether glaucoma severity modifies this relationship.

Design: Retrospective, longitudinal cohort study.

Participants: Two thousand nine hundred ninety-two OCT scans from 474 eyes of 241 patients with glaucoma or glaucoma suspect status.