Dataset Information

Phosphorylated tau sites that are elevated in Alzheimer's disease fluid biomarkers are visualized in early neurofibrillary tangle maturity levels in the post mortem brain.

ABSTRACT:

Introduction

Alzheimer's disease (AD) biomarkers are increasingly more reliable in predicting neuropathology. To facilitate interpretation of phosphorylated tau sites as an early fluid biomarker, we sought to characterize which neurofibrillary tangle maturity levels (pretangle, intermediary 1, mature tangle, intermediary 2, and ghost tangle) are recognized.

Methods

We queried the Florida Autopsied Multi-Ethnic (FLAME) cohort for cases ranging from Braak stages I through VI, excluding non-AD neuropathologies and tauopathies. Thioflavin-S staining was compared to immunohistochemical measures of phosphorylated threonine (pT) 181, pT205, pT217, and pT231 in two hippocampal subsectors across n = 24 cases.

Results

Each phosphorylated tau site immunohistochemically labeled early neurofibrillary tangle maturity levels compared to advanced levels recognized by thioflavin-S. Hippocampal burden generally increased with each Braak stage.

Discussion

These results provide neurobiologic evidence that these phosphorylated tau fluid biomarker sites are present during early neurofibrillary tangle maturity levels and may explain why these fluid biomarker measures are observed before symptom onset.

Highlights

Immunohistochemical evaluation of four phosphorylated tau fluid biomarker sites. Earlier neurofibrillary tangle maturity levels recognized by phosphorylated tau in proline-rich region. Advanced tangle pathology is elevated in the subiculum compared to the cornu ammonis 1 of the hippocampus. Novel semi-quantitative frequency to calculate tangle maturity frequency.

SUBMITTER: Moloney CM

PROVIDER: S-EPMC9895127 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Publications

Phosphorylated tau sites that are elevated in Alzheimer's disease fluid biomarkers are visualized in early neurofibrillary tangle maturity levels in the post mortem brain.

Moloney Christina M CM Labuzan Sydney A SA Crook Julia E JE Siddiqui Habeeba H Castanedes-Casey Monica M Lachner Christian C Petersen Ronald C RC Duara Ranjan R Graff-Radford Neill R NR Dickson Dennis W DW Mielke Michelle M MM Murray Melissa E ME

Alzheimer's & dementia : the journal of the Alzheimer's Association 20220803 3

<h4>Introduction</h4>Alzheimer's disease (AD) biomarkers are increasingly more reliable in predicting neuropathology. To facilitate interpretation of phosphorylated tau sites as an early fluid biomarker, we sought to characterize which neurofibrillary tangle maturity levels (pretangle, intermediary 1, mature tangle, intermediary 2, and ghost tangle) are recognized.<h4>Methods</h4>We queried the Florida Autopsied Multi-Ethnic (FLAME) cohort for cases ranging from Braak stages I through VI, exclud ...[more]

PMID: 35920592

Similar Datasets

Project description:Alzheimer's disease (AD) is pathologically characterized by the accumulation of amyloid-β (Aβ) plaques, neurofibrillary tangles and widespread neuronal loss in the brain. In recent years, blood biomarkers have emerged as a realistic prospect to highlight accumulating pathology for secondary prevention trials. Neurofilament light chain (NfL), a marker of axonal degeneration, is robustly elevated in the blood of many neurological and neurodegenerative conditions, including AD. A strong relationship with cerebrospinal fluid (CSF) NfL suggests that these biomarker modalities reflect the same pathological process. Yet, the connection between blood NfL and brain tissue pathology has not been directly compared. In this study, longitudinal plasma NfL from cognitively healthy controls (n = 12) and AD participants (n = 57) were quantified by the Simoa platform. On reaching post-mortem, neuropathological assessment was performed on all participants, with additional frozen and paraffin-embedded tissue acquired from 26 participants for further biochemical (Aβ1-42, Aβ1-40, tau) and histological (NfL) evaluation. Plasma NfL concentrations were significantly increased in AD and correlated with cognitive decline, independent of age. Retrospective stratification based on Braak staging revealed that baseline plasma NfL concentrations were associated with higher neurofibrillary tangle pathology at post-mortem. Longitudinal increases in plasma NfL were observed in all Braak groupings; a significant negative association, however, was found between plasma NfL at time point 1 and both its rate of change and annual percentage increase. Immunohistochemical evaluation of NfL in the medial temporal gyrus (MTG) demonstrated an inverse relationship between Braak stages and NfL staining. Importantly, a significant negative correlation was found between the plasma NfL measurement closest to death and the level of NfL staining in the MTG at post-mortem. For the first time, we demonstrate that plasma NfL associates with the severity of neurofibrillary tangle pathology and neurodegeneration in the post-mortem brain.

Dataset Information

Phosphorylated tau sites that are elevated in Alzheimer's disease fluid biomarkers are visualized in early neurofibrillary tangle maturity levels in the post mortem brain.

Introduction

Methods

Results

Discussion

Highlights

Publications

Phosphorylated tau sites that are elevated in Alzheimer's disease fluid biomarkers are visualized in early neurofibrillary tangle maturity levels in the post mortem brain.

Similar Datasets

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