Association of CSF α-synuclein seed amplification assay positivity with disease progression and cognitive decline: A longitudinal Alzheimer's Disease Neuroimaging Initiative study.

Introduction: Cerebrospinal fluid (CSF) α-synuclein (α-syn) seed amplification assay (SAA) is a sensitive and specific tool for detecting Lewy body co-pathology in Alzheimer's disease.

Methods: A total of 1637 cross-sectional and 407 longitudinal CSF samples from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were tested with SAA. We examined longitudinal dynamics of amyloid beta (Aβ), α-syn seeds, and phosphorylated tau181 (p-tau181), along with global and domain-specific cognition in stable SAA+, stable SAA-, and those who converted to SAA+ from SAA-.

Misfolded alpha synuclein co-occurrence with Alzheimer's disease proteinopathy.

Introduction: Multi-etiology dementia necessitates in-vivo markers of copathologies including misfolded -synuclein (syn). We measured misfolded syn aggregates (syn-seeds) via qualitative seed amplifcation assays (synSAA) and examined relationships with markers of Alzheimer's disease (AD).

Methods: Cerebrospinal fluid (CSF) was obtained from 420 participants in two Wisconsin AD risk cohorts (35% male; 91% cognitively unimpaired; mean (SD) age, 65.

Evaluation of Cerebrospinal Fluid α-Synuclein Seed Amplification Assay in Progressive Supranuclear Palsy and Corticobasal Syndrome.

Background: Seed amplification assay (SAA) testing has been developed as a biomarker for the diagnosis of α-synuclein-related neurodegenerative disorders.

Objective: The objective of this study was to assess the rate of α-synuclein SAA positivity in progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) and to analyze clinical and pathological features of SAA-positive and -negative cases.

Methods: A total of 96 cerebrospinal fluid samples from clinically diagnosed PSP (n = 59) and CBS (n = 37) cases were analyzed using α-synuclein SAA.

Association of CSF α-Synuclein Seed Amplification Assay Positivity with Disease Progression and Cognitive Decline: A Longitudinal Alzheimer's Disease Neuroimaging Initiative Study.

Introduction: CSF α-synuclein seed amplification assay (SAA) is a sensitive and specific tool for detecting Lewy body (LB) co-pathology in AD.

Methods: 1637 cross-sectional and 407 longitudinal CSF samples from ADNI were tested with SAA. We examined longitudinal dynamics of Aβ, α-synuclein seeds, and p-tau181, along with global and domain-specific cognition in stable SAA+, stable SAA-, and those who converted to SAA+ from SAA-.

A cross-sectional study of α-synuclein seed amplification assay in Alzheimer's disease neuroimaging initiative: Prevalence and associations with Alzheimer's disease biomarkers and cognitive function.

Introduction: Alzheimer's disease (AD) pathology is defined by β-amyloid (Aβ) plaques and neurofibrillary tau, but Lewy bodies (LBs; 𝛼-synuclein aggregates) are a common co-pathology for which effective biomarkers are needed.

Methods: A validated α-synuclein Seed Amplification Assay (SAA) was used on recent cerebrospinal fluid (CSF) samples from 1638 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants, 78 with LB-pathology confirmation at autopsy. We compared SAA outcomes with neuropathology, Aβ and tau biomarkers, risk-factors, genetics, and cognitive trajectories.

Colorectal Adenocarcinomas Harboring ALK Fusion Genes: A Clinicopathologic and Molecular Genetic Study of 12 Cases and Review of the Literature.

This study determined the frequency and the clinicopathologic and genetic features of colorectal carcinomas driven by oncogenic fusions of the anaplastic lymphoma kinase gene (ALK). Of the 8150 screened tumors, 12 (0.15%) were immunohistochemically ALK-positive with D5F3 antibody.

Colonic Adenocarcinomas Harboring NTRK Fusion Genes: A Clinicopathologic and Molecular Genetic Study of 16 Cases and Review of the Literature.

This study was undertaken to determine the frequency, and the clinicopathologic and genetic features, of colon cancers driven by neurotrophic receptor tyrosine kinase (NTRK) gene fusions. Of the 7008 tumors screened for NTRK expression using a pan-Trk antibody, 16 (0.23%) had Trk immunoreactivity.

Detecting Gene Rearrangements in Patient Populations Through a 2-Step Diagnostic Test Comprised of Rapid IHC Enrichment Followed by Sensitive Next-Generation Sequencing.

Targeted therapy combined with companion diagnostics has led to the advancement of next-generation sequencing (NGS) for detection of molecular alterations. However, using a diagnostic test to identify patient populations with low prevalence molecular alterations, such as gene rearrangements, poses efficiency, and cost challenges. To address this, we have developed a 2-step diagnostic test to identify NTRK1, NTRK2, NTRK3, ROS1, and ALK rearrangements in formalin-fixed paraffin-embedded clinical specimens.

The effect of environmental storage conditions on bone marrow fat determination in three species.

Diagnostic laboratories are frequently required to assess the antemortem nutritional condition of deceased animals. The percentage of fat in the bone marrow is used to diagnose starvation because this fat depot is typically the last in the body to be depleted. Diagnosticians rely on measurement of bone marrow adipose content using fat solvent-extraction methods; however, the effects of tissue storage conditions before processing have not been fully assessed.

Reduced receptor editing in lupus-prone MRL/lpr mice.

The initial B cell repertoire contains a considerable proportion of autoreactive specificities. The first major B cell tolerance checkpoint is at the stage of the immature B cell, where receptor editing is the primary mode of eliminating self-reactivity. The cells that emigrate from the bone marrow have a second tolerance checkpoint in the transitional compartment in the spleen.

Mice expressing HLA-DQ6alpha8beta transgenes develop polychondritis spontaneously.

Relapsing polychondritis (RP) is a human autoimmune disease of unknown etiology in which cartilaginous sites are destroyed by cyclic inflammatory episodes beginning, most commonly, during the fourth or fifth decade of life. We have previously described collagen-induced polychondritis that closely mirrors RP occurring in young (6-8 weeks old) HLA-DQ6alphabeta 8alphabeta transgenic Abeta0 mice, following immunization with heterologous type II collagen (CII). We present evidence here that transgenic strains expressing the DQ6alpha8beta transgene develop spontaneous polychondritis (SP) at the mouse equivalent of human middle age (4.