Embedding Brain Tissue for Routine Histopathology: A Processing Step Worthy of Consideration in the Digital Pathology Era.

The importance of technical quality for histopathologic examination has only increased in recent years with the expanding use of digital pathology. The University of Kentucky Alzheimer's Disease Center (UK-ADC) Neuropathology Core has decades of experience with brain histopathology and has emphasized the importance of quantitative assessments of histopathologic hallmarks. Technical artifacts and nonuniform samples are challenging for high-throughput digital analyses after the slides have been scanned, so that methodological optimization may be helpful.

Alzheimer Disease Pathology-Associated Polymorphism in a Complex Variable Number of Tandem Repeat Region Within the MUC6 Gene, Near the AP2A2 Gene.

We found evidence of late-onset Alzheimer disease (LOAD)-associated genetic polymorphism within an exon of Mucin 6 (MUC6) and immediately downstream from another gene: Adaptor Related Protein Complex 2 Subunit Alpha 2 (AP2A2). PCR analyses on genomic DNA samples confirmed that the size of the MUC6 variable number tandem repeat (VNTR) region was highly polymorphic. In a cohort of autopsied subjects with quantitative digital pathology data (n = 119), the size of the polymorphic region was associated with the severity of pTau pathology in neocortex.

The Amygdala as a Locus of Pathologic Misfolding in Neurodegenerative Diseases.

Over the course of most common neurodegenerative diseases the amygdala accumulates pathologically misfolded proteins. Misfolding of 1 protein in aged brains often is accompanied by the misfolding of other proteins, suggesting synergistic mechanisms. The multiplicity of pathogenic processes in human amygdalae has potentially important implications for the pathogenesis of Alzheimer disease, Lewy body diseases, chronic traumatic encephalopathy, primary age-related tauopathy, and hippocampal sclerosis, and for the biomarkers used to diagnose those diseases.