Early astrocytosis in autosomal dominant Alzheimer’s disease measured in vivo by multi-tracer positron emission tomography

• Published in: Scientific reports Vol. 5; no. 1; p. 16404
• Main Authors: Schöll, Michael, Carter, Stephen F., Westman, Eric, Rodriguez-Vieitez, Elena, Almkvist, Ove, Thordardottir, Steinunn, Wall, Anders, Graff, Caroline, Långström, Bengt, Nordberg, Agneta
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10-11-2015; Nature Publishing Group
• Subjects: 59; 59/78; 692/53/2421; 692/617/375/132/1283; Age of Onset; Aged; Alzheimer Disease - diagnosis; Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer Disease - psychology; Alzheimer's disease; Amyloid beta-Peptides - metabolism; Astrocytes; Autopsy; Cognitive ability; Cognitive Dysfunction; compound b; Deuterium; diagnosis; dynamic biomarkers; Emission measurements; Female; Fluorodeoxyglucose F18; Genes, Dominant; Genotype; Gliosis; Gliosis - genetics; Gliosis - pathology; Glucose metabolism; human brain; Humanities and Social Sciences; Humans; hypothetical model; Inflammation; Male; Medicin och hälsovetenskap; Memory, Episodic; Middle Aged; mild cognitive impairment; monoamine-oxidase-b; multidisciplinary; Multivariate analysis; Mutation; Neurodegenerative diseases; neuroinflammation; Neuropsychological Tests; Neurosciences; Neurovetenskaper; pet; Plaque, Amyloid - metabolism; Plaque, Amyloid - pathology; Positron emission tomography; Positron-Emission Tomography - methods; Principal Component Analysis; Radioactive tracers; Retention; Science; Selegiline; Senile plaques; Studies; ykl-40; β-Amyloid
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep16404

Studying autosomal dominant Alzheimer’s disease (ADAD), caused by gene mutations yielding nearly complete penetrance and a distinct age of symptom onset, allows investigation of presymptomatic pathological processes that can identify a therapeutic window for disease-modifying therapies. Astrocyte activation may occur in presymptomatic Alzheimer’s disease (AD) because reactive astrocytes surround β-amyloid (Aβ) plaques in autopsy brain tissue. Positron emission tomography was performed to investigate fibrillar Aβ, astrocytosis and cerebral glucose metabolism with the radiotracers
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C-Pittsburgh compound-B (PIB),
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C-deuterium-L-deprenyl (DED) and
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F-fluorodeoxyglucose (FDG) respectively in presymptomatic and symptomatic ADAD participants (n = 21), patients with mild cognitive impairment (n = 11) and sporadic AD (n = 7). Multivariate analysis using the combined data from all radiotracers clearly separated the different groups along the first and second principal components according to increased PIB retention/decreased FDG uptake (component 1) and increased DED binding (component 2). Presymptomatic ADAD mutation carriers showed significantly higher PIB retention than non-carriers in all brain regions except the hippocampus. DED binding was highest in presymptomatic ADAD mutation carriers. This suggests that non-fibrillar Aβ or early stage plaque depostion might interact with inflammatory responses indicating astrocytosis as an early contributory driving force in AD pathology. The novelty of this finding will be investigated in longitudinal follow-up studies.