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Tau Deposition as Measured by 3H-THK5117 in Cortical Layers of Post-Mortem Alzheimer’s Disease Brain in Comparison with Amyloid Plaques and Astrocytosis
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
2015 (English)Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesisAlternative title
Distribution av tau i hjärnbarkens lager i postmortal Alzheimerhjärna i jämförelse med amyloida plack och astrocytos (Swedish)
Abstract [en]

In Alzheimer’s disease (AD), a pathological aggregation of amyloid-β (Aβ) to Aβ plaques and of tau to neurofibrillary tangles occurs in the brain of the afflicted patient. These proteins are together with inflammatory processes such as astrocytosis considered as pathological hallmarks of AD. The advent of computerized imaging techniques such as Positron Emission Imaging (PET) has offered a non-invasive way of looking into the brain and has become a central tool in AD research and clinical assessment. PET radiotracers that specifically bind to AD pathological features have been developed.

Neurons of the human cerebral cortex are organized into typically six layers. Projections between cortical regions are originating and terminating in specific layers. As tau has been suggested to spread between interconnected neurons trans-synaptically, studying the deposition of tau in the cortical layers is of great importance for understanding tau’s spreading patterns within the brain. Furthermore, by comparing the laminar distribution of tau, Aβ and astrocytosis, the possible relationship between these pathological features can be understood.

The laminar distribution of hyperphosphorylated tau, reactive astrocytes and fibrillar Aβ were assessed using the radiotracers 3H-THK5117, 3H-L-deprenyl and 3H-PiB, respectively. The binding of each radiotracer through the cortical layers of an AD patient was quantified using ImageJ. The analysis was carried out on autoradiograms of post-mortem whole hemisphere brain sections.

Both 3H-THK5117 and 3H-L-deprenyl show laminar binding distributions, whereas 3H-PIB has a more even distribution between different cortical layers. The similarities and dissimilarities between these pathological markers in different cortical layers illustrate the complexity of AD pathology. Preliminary data on two other AD cases present somewhat different laminar binding distributions. This interindividual variability is an important aspect of AD.

Abstract [sv]

Alzheimers sjukdom är den största neurodegenerativa sjukdomen och den vanligaste demenssjukdomen. Ansamling av amyloid-β till amyloida plack och tau till neuro-fibrillära tangles utgör, tillsammans med inflammatoriska förändringar som astrocytos, de karaktäristiska patologiska förändringarna i hjärnan associerade med sjukdomen. Radioaktivt märkta ämnen, radioligander, som binder specifikt till dessa patologiska markörer har utvecklats för PET-studier på Alzheimerpatienter.

Hjärnbarken är indelad i regioner som består av nervceller i sex lager. Mellan regionerna finns kopplingar som utgår och når specifika lager. Genom att studera distributionen av patologiska förändringar i dessa lager kan en ökad förståelse fås för hur sjukdomen sprids i hjärnan, samt huruvida dessa patologiska processer är relaterade.

Bindningen av 3H-THK5117 (tau), 3H-L-deprenyl (reaktiva astrocyter) och 3H-PiB (amyloida plack) mättes tvärsigenom hjärnbarkens lager med programmet ImageJ. Analysen utfördes på autoradiogram av postmortal hjärnvävnad från en avliden Alzheimerpatient.

Både tau och astrocytos har en tydlig lagerfördelning, medan amyloida plack har en mer jämt fördelad utbredning. Likheter och skillnader mellan dessa patologiska markörer i hjärnbarkens lager illustrerar hur komplex Alzheimers sjukdom är. Preliminära data från två andra patienter uppvisar även individuella variationer, vilket är en viktig aspekt av sjukdomen.

Place, publisher, year, edition, pages
2015. , 35 p.
Keyword [en]
Alzheimer's disease, tau, amyloid, astrocytosis, cortex, layers
Keyword [sv]
Alzheimers sjukdom, tau, amyloid, astrocytos, kortex, lager
National Category
Pharmaceutical Sciences
URN: urn:nbn:se:uu:diva-242537OAI: oai:DiVA.org:uu-242537DiVA: diva2:783769
External cooperation
Karolinska Institutet, Institutionen för NVS, Centrum för Alzheimerforskning, Sektionen för Translationell Alzheimer Neurobiologi, Novum, Stockholm
Subject / course
Pharmaceutical Pharmacology
Educational program
Master of Science Programme in Pharmacy
Available from: 2015-02-02 Created: 2015-01-27 Last updated: 2015-02-02Bibliographically approved

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