Increased plasma neurofilament light chain concentration correlates with severity of post-mortem neurofibrillary tangle pathology and neurodegeneration

You will need your doctor to figure out prevention protocols for Alzheimers, dementia and Parkinsons.  YOUR DOCTORS' RESPONSIBILITY!

The reason you need dementia prevention: 

1. A documented 33% dementia chance post-stroke from an Australian study?   May 2012.

2. Then this study came out and seems to have a range from 17-66%. December 2013.

3. A 20% chance in this research.   July 2013.

4. Dementia Risk Doubled in Patients Following Stroke September 2018 

5. Parkinson’s Disease May Have Link to Stroke March 2017

 

Increased plasma neurofilament light chain concentration correlates with severity of post-mortem neurofibrillary tangle pathology and neurodegeneration

• Nicholas J. Ashton
• Antoine Leuzy
• Yau Mun Lim
• Claire Troakes
• Tibor Hortobágyi
• Kina Höglund
• Dag Aarsland
• Simon Lovestone
• Michael Schöll
• Kaj Blennow
• Henrik Zetterberg
• Abdul Hye

• Nicholas J. Ashton
  • 1
  • 2
  • 3
  • 4
• Antoine Leuzy
  • 1
  • 2
• Yau Mun Lim
  • 3
  • 4
• Claire Troakes
  • 3
  • 4
• Tibor Hortobágyi
  • 3
  • 5
• Kina Höglund
  • 1
• Dag Aarsland
  • 3
  • 4
  • 6
• Simon Lovestone
  • 7
• Michael Schöll
  • 1
  • 8
  • 9
• Kaj Blennow
  • 1
  • 10
• Henrik Zetterberg
  • 1
  • 10
  • 11
  • 12
• Abdul Hye
  • 3
  • 4
  Email author

1. 1.Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiologythe Sahlgrenska Academy at the University of GothenburgMölndalSweden
2. 2.Wallenberg Centre for Molecular and Translational MedicineUniversity of GothenburgGothenburgSweden
3. 3.King’s College London, Institute of Psychiatry, Psychology & NeuroscienceMaurice Wohl Clinical Neuroscience InstituteLondonUK
4. 4.NIHR Biomedical Research Centre for Mental Health & Biomedical Research Unit for Dementia at South London & Maudsley NHS FoundationLondonUK
5. 5.MTA-DE Cerebrovascular and Neurodegenerative Research Group, Department of NeurologyUniversity of DebrecenDebrecenHungary
6. 6.Centre for Age-Related MedicineStavanger University HospitalStavangerNorway
7. 7.Department of PsychiatryUniversity of Oxford. Warneford HospitalOxfordUK
8. 8.Clinical Memory Research Unit, Department of Clinical Sciences, MalmöLund UniversityLundSweden
9. 9.Department of Neurodegenerative DiseaseUCL Institute of NeurologyLondonUK
10. 10.Clinical Neurochemistry LaboratorySahlgrenska University HospitalMölndalSweden
11. 11.Department of Molecular NeuroscienceUCL Institute of NeurologyQueen SquareUK
12. 12.UK Dementia Research Institute at UCL|LondonUK

Open Access

Research

First Online: 09 January 2019

Abstract

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 (Aβ_1–42, Aβ_1–40, 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.