Neuroinflammation and Tau Colocalize in vivo in Progressive Supranuclear Palsy.

Abstract

OBJECTIVE:

We examined the relationship between tau pathology and neuroinflammation using [11 C]PK11195 and [18 F]AV-1451 PET in 17 patients with progressive supranuclear palsy (PSP) Richardson's syndrome. We tested the hypothesis that neuroinflammation and tau protein aggregation colocalize macroscopically, and correlate with clinical severity.

METHODS:

Nondisplaceable binding potential (BPND ) for each ligand was quantified in 83 regions of interest (ROIs). The [11 C]PK11195 and [18 F]AV-1451 BPND values were correlated across all regions. The spatial distributions of [11 C]PK11195 and [18 F]AV-1451 binding were determined by principal component analyses (PCAs), and the loading of each spatial component compared against the patients' clinical severity (using the PSP rating scale).

RESULTS:

Regional [11 C]PK11195 and [18 F]AV-1451 binding were positively correlated (R = 0.577, p < 0.0001). The PCA identified 4 components for each ligand, reflecting the relative expression of tau pathology or neuroinflammation in distinct groups of brain regions. Positive associations between [11 C]PK11195 and [18 F]AV-1451 components' loadings were found in both subcortical (R = 0.769, p < 0.0001) and cortical regions (R = 0.836, p < 0.0001). There were positive correlations between clinical severity and both subcortical tau pathology (R = 0.667, p = 0.003) and neuroinflammation (R = 0.788, p < 0.001).

INTERPRETATION:

We show that tau pathology and neuroinflammation colocalize in PSP, and that individual differences in subcortical tau pathology and neuroinflammation are linked to clinical severity. Although longitudinal studies are needed to determine causal associations between these molecular pathologies, we suggest that the combination of tau- and immune-oriented strategies may be useful for effective disease-modifying treatments in PSP. ANN NEUROL 2020;88:1194-1204.

• Authors: Maura Malpetti, Luca Passamonti, Timothy Rittman, P Simon Jones, Patricia Vázquez Rodríguez, W Richard Bevan-Jones, Young T Hong, Tim D Fryer, Franklin I Aigbirhio, John T O'Brien, James B Rowe
• Journal: Annals of neurology (Ann Neurol) Vol. 88 Issue 6 Pg. 1194-1204 (12 2020) ISSN: 1531-8249 [Electronic] United States
• PMID: 32951237 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.

Chemical References

• Carbolines
• Carbon Radioisotopes
• Inflammation Mediators
• Isoquinolines
• tau Proteins
• 7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole
• PK 11195

Topics

• Aged
• Brain (metabolism)
• Carbolines (metabolism)
• Carbon Radioisotopes
• Female
• Humans
• Inflammation Mediators (metabolism)
• Isoquinolines (metabolism)
• Magnetic Resonance Imaging
• Male
• Neuroimaging
• Positron-Emission Tomography
• Severity of Illness Index
• Supranuclear Palsy, Progressive (metabolism)
• tau Proteins (metabolism)