bioRxiv Science⌕ Search

Biology subjects

Ehrenberg, A. J.

Publications and source records attributed to Ehrenberg, A. J..

2 recordsLinked to original sources
bioRxiv2019

Multiplex immunofluorescence methods in neurodegenerative diseases

The application of multiplex immunofluorescence to human post-mortem tissue would drive observational studies of selective vulnerability in neurodegenerative proteinopathies. Efficient elution of antibodies is critical for flexibility of antibody combinations and the ability to utilize a sample in multiple rounds of immunostaining. Here, we test two elution strategies for antibodies relevant to the study of selective vulnerability in neurodegenerative diseases in post-mortem human samples from both long-fixed and short-fixed tissue. Both 2-Mercaptoethanol/SDS-based and Urea/SDS/Glycine-based elution strategies work well with the antibodies selected, confirming observations from previous studies with other antibody types.

pathology↗
bioRxiv2019

Alzheimer's disease clinical variants show distinct regional patterns of neurofibrillary tangle accumulation

BackgroundNeurofibrillary tangle (NFT) pathology in Alzheimers disease (AD) follows a stereotypic progression well-characterized by Braak staging. However, some AD cases show deviations from the Braak staging scheme. In this study, we tested the hypothesis that these variations in the regional distribution of tau pathology are linked to heterogeneity in the clinical phenotypes of AD. MethodsWe included a clinicopathological cohort of ninety-four AD cases enriched for atypical clinical presentations. Subjects underwent apolipoprotein E (APOE) genotyping and neuropsychological testing. Main cognitive domains (executive, visuospatial, language, and memory function) were assessed using an established composite z-score. We assessed NFT density and distribution from thioflavin S fluorescent microscopy throughout four neocortical and two hippocampal regions. A mathematical algorithm classifying AD cases into typical, hippocampal sparing (HpSp), and limbic predominant (LP) subtypes based on regional NFT burden was compared to unbiased hierarchical clustering for cases with Braak stage > IV. ResultsPatients diagnosed with logopenic primary progressive aphasia showed significantly higher NFT density in the superior temporal gyrus relative to patients diagnosed with Alzheimer-type dementia (p = 0.0091), while patients with corticobasal syndrome showed significantly higher NFT density in the primary motor cortex (p = 0.0205). Hierarchical clustering identified three discrete clusters of patients characterized respectively by low overall NFT burden (n = 18), high overall burden (n = 30), and cortical-predominant burden (n = 24). A regionally specific effect was observed for visuospatial ability; higher NFT density in the angular gyrus ({beta} = - 0.0921, p = 0.0099) and in the CA1 sector of the hippocampus ({beta} = -0.0735, p = 0.0380) was significantly associated with more severe visuospatial dysfunction, modulated by age of death. ConclusionsOur results suggest domain-specific functional consequences of regional NFT accumulation. In particular, we observed focal aggregation of NFT density in clinically relevant regions among different clinical AD variants. Continued work to map the regionally specific clinical consequences of tau accumulation presents an opportunity to increase understanding of disease mechanisms underlying atypical clinical manifestations.

pathology↗