Astrocytosis measured by ¹¹C-deprenyl PET correlates with decrease in gray matter density in the parahippocampus of prodromal Alzheimer's patients.

Abstract

PURPOSE:

The Alzheimer's disease (AD) pathology is characterized by fibrillar amyloid deposits and neurofibrillary tangles, as well as the activation of astrocytosis, microglia activation, atrophy, dysfunctional synapse, and cognitive impairments. The aim of this study was to test the hypothesis that astrocytosis is correlated with reduced gray matter density in prodromal AD.

METHODS:

Twenty patients with AD or mild cognitive impairment (MCI) underwent multi-tracer positron emission tomography (PET) studies with (11)C-Pittsburgh compound B ((11)C-PIB), (18) F-Fluorodeoxyglucose ((18) F-FDG), and (11)C-deuterium-L-deprenyl ((11)C-DED) PET imaging, as well as magnetic resonance imaging (MRI) scanning, cerebrospinal fluid (CSF) biomarker analysis, and neuropsychological assessments. The parahippocampus was selected as a region of interest, and each value was calculated for four different imaging modalities. Correlation analysis was applied between DED slope values and gray matter (GM) densities by MRI. To further explore possible relationships, correlation analyses were performed between the different variables, including the CSF biomarker.

RESULTS:

A significant negative correlation was obtained between DED slope values and GM density in the parahippocampus in PIB-positive (PIB + ve) MCI patients (p = 0.025) (prodromal AD). Furthermore, in exploratory analyses, a positive correlation was observed between PIB-PET retention and DED binding in AD patients (p = 0.014), and a negative correlation was observed between PIB retention and CSF Aβ42 levels in MCI patients (p = 0.021), while the GM density and CSF total tau levels were negatively correlated in both PIB + ve MCI (p = 0.002) and MCI patients (p = 0.001). No significant correlation was observed with FDG-PET and with any of the other PET, MRI, or CSF biomarkers.

CONCLUSIONS:

High astrocytosis levels in the parahippocampus of PIB + ve MCI (prodromal AD) patients suggest an early preclinical influence on cellular tissue loss. The lack of correlation between astrocytosis and CSF tau levels, and a positive correlation between astrocytosis and fibrillar amyloid deposition in clinical demented AD together indicate that parahippocampal astrocytosis might have some causality within the amyloid pathology.

• Authors: I L Han Choo, Stephen F Carter, Michael L Schöll, Agneta Nordberg
• Journal: European journal of nuclear medicine and molecular imaging (Eur J Nucl Med Mol Imaging) Vol. 41 Issue 11 Pg. 2120-6 (Nov 2014) ISSN: 1619-7089 [Electronic] Germany
• PMID: 25077930 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carbon Radioisotopes
• Selegiline

Topics

• Alzheimer Disease (complications)
• Carbon Radioisotopes
• Female
• Gliosis (complications, diagnostic imaging, pathology)
• Gray Matter (diagnostic imaging, pathology)
• Hippocampus (diagnostic imaging, pathology)
• Humans
• Male
• Middle Aged
• Organ Size
• Positron-Emission Tomography
• Prodromal Symptoms
• Selegiline