Astrocytosis measured by 11C-deprenyl PET correlates with decrease in gray matter density in the parahippocampus of prodromal Alzheimer’s patients
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.
Twenty patients with AD or mild cognitive impairment (MCI) underwent multi-tracer positron emission tomography (PET) studies with 11C-Pittsburgh compound B (11C-PIB), 18 F-Fluorodeoxyglucose (18 F-FDG), and 11C-deuterium-L-deprenyl (11C-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.
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.
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.
KeywordsMild cognitive impairment Astrocytosis Amyloid deposition Gray matter density Parahippocampus Multi-tracer PET imaging Alzheimer’s disease
The present article was funded by the following grants: the Swedish Research Council (project 05817), the Strategic Research Program in Neuroscience at Karolinska Institutet, the Swedish Brain Power, the Old Servants foundation, the Gun and Bertil Stohne’s foundation, the Alzheimer Foundation in Sweden, the Brain Foundation, the Regional Agreement on Medical Training and Clinical Research (ALF) between Stockholm County Council and the Karolinska Institutet, INMIND (grant agreement number 278850, resources) of the European Union’s Seventh Framework Programme for Research and Technological Development (FP7/2007-2013), and the research fund from Chosun University (K206556001-1).
None of the authors have any actual or potential conflicts of interest.
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