Assessing Reactive Astrocytosis in Alzheimer's Disease Using [18F]Fluorodeprenyl-D2 PET Imaging

1992 

Abstract Submission 

Boris-Stephan Rauchmann¹, Selim Gürsel², Carolin Kurz², Simon Lindner³, Nicolai Franzmeier⁴, Katharina Buerger⁵, Johannes Gnörich³, Mirlind Zaganjori⁵, Letitia Vogler³, Laura Sanzo³, Klaus Seelos⁶, Robert Perneczky⁷, Matthias Brendel³

¹University Hospital, LMU Munich, München, Deutschland, ²Department of Psychiatry and Psychotherapy, University Hospital, Technical University Munich, Munich, Munich, Germany, ³Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany, Munich, Germany, ⁴University Hospital LMU Munich, Munich, Bavaria, ⁵Institute for Stroke and Dementia Research, University Hospital, LMU Munich, Munich, Germany, Munich, Germany, ⁶Institute of Neuroradiology, University Hospital, LMU Munich, Munich, Germany, Munich, Germany, ⁷German Centre for Neurodegenerative Diseases (DZNE), Munich, Germany

Boris-Stephan Rauchmann  
University Hospital, LMU Munich
München, Deutschland

Selim Gürsel  
Department of Psychiatry and Psychotherapy, University Hospital, Technical University Munich, Munich
Munich, Germany

Carolin Kurz  
Department of Psychiatry and Psychotherapy, University Hospital, Technical University Munich, Munich
Munich, Germany

Simon Lindner  
Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany
Munich, Germany

Nicolai Franzmeier  
University Hospital LMU Munich
Munich, Bavaria

Katharina Buerger  
Institute for Stroke and Dementia Research, University Hospital, LMU Munich, Munich, Germany
Munich, Germany

Johannes Gnörich  
Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany
Munich, Germany

Mirlind Zaganjori  
Institute for Stroke and Dementia Research, University Hospital, LMU Munich, Munich, Germany
Munich, Germany

Letitia Vogler  
Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany
Munich, Germany

Laura Sanzo  
Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany
Munich, Germany

Klaus Seelos  
Institute of Neuroradiology, University Hospital, LMU Munich, Munich, Germany
Munich, Germany

Robert Perneczky  
German Centre for Neurodegenerative Diseases (DZNE)
Munich, Germany

Matthias Brendel  
Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany
Munich, Germany

The progression of Alzheimer's Disease (AD), the most common cause of the dementia, is often accompanied by neuroinflammation, which manifests prior to significant cognitive decline. Reactive astrocytosis is a hallmark of such inflammation, potentially serving as an early biomarker for AD pathology (1). Our study employs [18F]fluorodeprenyl-D2 ([18F]F-DED) positron emission tomography (PET) imaging to in vivo quantify astrocytosis comparing AD with healthy controls and examines its correlation with cognitive deterioration in AD.

We conducted a cross-sectional analysis involving 12 patients within the early stages of the AD spectrum and 11 cognitively healthy controls. All participants underwent [18F]F-DED and MRI imaging. AD patients were identified based on CSF amyloid-β42/40 ratios below 5.5% and Mini-Mental State Examination (MMSE) score below 27. Controls scored 27 or higher on the MMSE and displayed no amyloid-β pathology. Differences in [18F]F-DED uptake between groups were evaluated through region-of-interest (ROI)-based analyses. The preprocessing of [18F]F-DED data was performed in PMOD software, and the quantification of cortical uptake was determined by computing the volume of distribution, which is the ratio of the radioligand concentration in target tissue (expressed in kBq/cm³) to that in the image derived plasma (in kBq/mL) at equilibrium. In a ROI based analysis we employed the Automated Anatomical Labeling (AAL) atlas, which was adapted to individual gray matter masks and then conformed to the individual [18F]F-DED maps. We computed the median uptake value for each ROI. Cortical amyloid deposition was measured using [18F]flutemetamol β-amyloid-PET imaging. Cerebrospinal fluid (CSF) biomarkers, including Aβ42, Aβ40, and phosphorylated tau (p-tau), were measured using the Lumipulse G1200 platform from Fujirebio. Cognitive performance was tested using the Mini-Mental State Examination (MMSE). We explored the associations between cognitive performance metrics and [18F]F-DED uptake utilizing linear regression models, controlling for age and sex, conducted in the R statistical environment.

The study involved participants with an average age of 71, featuring an equal distribution of genders. Notably, we detected a pronounced increase in [18F]F-DED uptake in Alzheimer's Disease (AD) impacted areas, specifically in the bilateral occipital (Left: T:2.28, p=0.03; Right: T:2.51, p=0.02), temporal (Left: T:2.21, p=0.03; Right: T:2.22, p=0.03), and frontal lobes (Left: T:2.46, p<0.02; Right: T:2.45, p<0.02). These uptakes were significantly correlated with cognitive assessments. Specifically, enhanced uptake in the temporal regions was strongly linked to lower cerebrospinal fluid amyloid-β ratios and reduced scores on the Mini-Mental State Examination (MMSE) (p<0.01). These relationships persisted after adjusting for age and gender factors.

Our findings suggest that [18F]F-DED PET imaging can detect reactive astrocytosis in regions vulnerable to AD pathology, potentially before the onset of severe cognitive symptoms. The correlation between increased tracer uptake and cognitive decline reinforces the utility of [18F]F-DED as a biomarker for AD progression. These insights into the spatial patterns of neuroinflammation offer a promising avenue for early diagnosis and monitoring of AD, paving the way for interventions that target neuroinflammatory processes in the disease's early stages.

Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) ²

Working Memory

Aging

PET Modeling and Analysis ¹

Memory

Positron Emission Tomography (PET)

Other - Alzheimers Disease