Amyloid Biologie

The group studies mechanisms of amyloid formation, in particular the molecular nature of pathogenic protein aggregation.

Main objectives
Recent results

1. To determine which forms of Aβ can cause protein aggregation and amyloid formation.

2. To establish the subcellular localization of Aβ and the mechanisms by which they induce amyloidogenesis.

3. To determine the environmental requirements and mechanisms underlying the self-replication of pathogenic Aβ aggregates.

To achieve these goals, we are developing biochemical protocols to isolate different soluble and membrane-associated Aβ aggregates. We determine their amyloid inducing properties and toxicity with a combination of in vitro assays and in vivo genetically engineered mouse models.

β-amyloid-containing brain tissue has previously been shown to stimulate Aβ deposition in Aβ precursor protein- (APP) transgenic mice, a process termed Aβ seeding. Seeding activity was found in crude insoluble and soluble fractions but little is known about the nature and diversity of the seeds. For rapid in vitro screening of brain fractions we established a medium-throughput assay that quantifies Aβ seeds based on their enhancement of Aβ aggregation. Combining differential and sucrose gradient centrifugation, we have identified distinct Aβ seed-containing membrane fractions in brain homogenates from APP-transgenic mice (Marzesco et al., Sci Reports 2015). The nature of the seeding activity in the soluble brain fraction is analyzed in a collaborative study using size-exclusion chromatography.

Consistent with the robust seeding activity of membrane fractions of Aβ in vitro and recent work from the prion field, lipids have come into focus as a key component supporting the aggregation. Furthermore, membranes and membrane anchoring proved to be key features of neurotoxicity in prion diseases. To investigate whether the membrane association of Aβ would alter aggregation and neurotoxicity in vivo we have established a transgenic mouse model expressing Aβ with a phospholipid membrane anchor. Crossbreeding APP-transgenic mice demonstrated that membrane-anchored Aβ promotes plaque deposition and increases neurodegeneration in vivo (Nagarathinam et al. J. Neurosci. 2013). Membrane lesions found in prion-affected mice were not replicated in double transgenic young mice which were clinically still healthy but Aβ-peptides were shown to accumulate on morphologically normal neurite membranes and elicited rapid glial recognition (Jeffrey et al. Neuropathol Appl Neurobiol. 2014). Future work will employ the role of membrane-anchored Aβ intermediates in the initiation of Aβ aggregation and neurotoxicity.

Contact: Frank Baumann, Matthias Staufenbiel  



Dr. Frank Baumann
Dr. Frank Baumann Research Group Leader
Molecular Biology
07071 29-81957 
 Anika Bühler
Anika Bühler Technical Assistant
Molecular Biology
07071 29-86857 
Dr. Matthias Staufenbiel
Dr. Matthias Staufenbiel Research Consultant
Molecular Biology

Groh N, Bühler A, Huang C, Li KW, vna Nierop P, Smit AB, Fandrich M, Baumann F, David DC, (2017) Age-Dependent Protein Aggregation Initiates Amyloid-beta Aggregation. Front Aging Neurosci 9: 138 (Abstract)

Marzesco AM, Flötenmeyer M, Bühler A, Obermüller U, Staufenbiel M, Jucker M, Baumann F (2016) Highly potent intracellular membrane-associated Aβ seeds. Sci Rep 6: 28125 (Abstract)

Jeffrey M, McGovern G, Barron R, Baumann F (2015) Membrane pathology and microglial activation of mice expressing membrane anchored or membrane released forms of Abeta and mutated human APP. Neuropathol Appl Neurobiol 41:458-70 (Abstract)

Nagarathinam A, Höflinger P, Bühler A, Schäfer C, McGovern G, Jeffrey M, Staufenbiel M, Jucker M, Baumann F (2013) Membrane-anchored Aβ accelerates amyloid formation and exacerbates amyloid-associated toxicity in mice. J Neuroscience 33:19284-94 (Abstract)

Dr. Frank Baumann Anschrift

Zentrum für Neurologie
Hertie-Institut für klinische Hirnforschung
Abteilung Zellbiologie neurologischer Erkrankungen

Otfried-Müller-Straße 27
72076 Tübingen

Tel.: +49 (0)7071 29-81957
Fax: +49 (0)7071 29-4521