Jürgen Götz on Could Disposing of Damaged Mitochondria Treat Alzheimer’s Disease?

COMMENT We share the view of Drs. Tapias and Beal that misfolded proteins such as Aβ and tau impair all aspects of mitochondrial functions. In fact, we have a long-standing interest in how Aβ and tau impair neuronal functions, dating back to 2005 when we combined ...

Jürgen Götz on Tau Stymies Transport Through Neuron’s Nucleus

COMMENT I really liked this study, which elegantly combines work in human and transgenic tissue, in vitro and in primary cultures. The human brain and doxycycline rescue experiments in rTg4510 mice are especially compelling. I think the question (admittedly a ...

Jürgen Götz on Bon Appétit: Endogenous Antibodies Prod Microglia to Eat Aβ Deposits

COMMENT This is a very interesting paper. In her news piece Madolyn Rogers writes “It is unclear how the antibodies enter the brain. The authors found no breach of the blood-brain barrier, but did see the antibody accumulate in the choroid plexus of 5xFAD mice, ...

Jürgen Götz on Does the Blood-Brain Barrier Stand Up to Alzheimer’s? Study Finds No Breach

COMMENT It is comforting to see that Bien-Ly and colleagues report on the absence of widespread BBB disruption in AD mouse models and that they further find that the levels of brain infarcts are similar in AD cases and healthy controls. We have recently become ...

Jürgen Götz on New Role For PICALM: Flushing Aβ From the Brain

COMMENT This is a nice study illustrating the point that assisting in the clearance of Aβ, in addition to preventing its formation, presents a suitable avenue for therapeutic interventions. Together with a study we have published recently (Leinenga and Götz, 2015 ...

Jürgen Götz on Scanning ultrasound removes amyloid-β and restores memory in an Alzheimer's disease mouse model.

COMMENT We are currently doing experiments to address some of the issues that have been raised by Dr. Landreth. There is a wealth of data established in species ranging from rodents to macaques, showing that ultrasound allows for a safe opening of the BBB (some ...

Jürgen Götz on Activity-dependent tau protein translocation to excitatory synapse is disrupted by exposure to amyloid-beta oligomers.

COMMENT I enjoyed reading this paper. The study adds to the notion that a prime function of tau is that of a scaffolding protein, not only in the axon but also in the dendrite where tau interacts, as this study shows, also with filamentous actin. Interesting is ...

Jürgen Götz on Sustained peripheral depletion of amyloid-β with a novel form of neprilysin does not affect central levels of amyloid-β.

COMMENT A very elegant study done in mice, rats, and monkeys showing that clearance of Aβ from the brain is most likely not because of a sink effect between this organ and the periphery. j.goetz 0 ...

Jürgen Götz on Soluble pathological tau in the entorhinal cortex leads to presynaptic deficits in an early Alzheimer's disease model.

COMMENT This is an interesting paper that supports our findings in mouse models and cell lines that soluble tau is toxic, as evidenced by the trapping of the kinesin adapter protein JIP1 in the soma under conditions where tau levels (irrespective of a pathogenic ...

Jürgen Götz on Two novel tau antibodies targeting the 396/404 region are primarily taken up by neurons and reduce tau pathology.

COMMENT An important study emphasising the validity of a tau-based immunotherapeutic approach in AD. j.goetz 0 ...

Jürgen Götz on Amyloid-β oligomers induce synaptic damage via Tau-dependent microtubule severing by TTLL6 and spastin.

COMMENT Using state-of-the-art technology, the Mandelkow team presents a very detailed analysis of how Aβ oligomers damage synapses. One of their most interesting findings is that the tau that accumulates in the somatodendritic domain of primary neurons exposed ...

Jürgen Götz on Proteomics Point to RNA Splicing Defects in Alzheimer’s

COMMENT This is interesting also in the context of our finding that in the presence of tau the splicing factor SFPQ is relocalized from the nucleus to the cytoplasm. j.goetz 0 Tau-mediated nuclear depletion and cytoplasmic accumulation of SFPQ in Alzheimer's ...

Jürgen Götz on Pooled GWAS Reveals New Alzheimer’s Genes and Pathways

COMMENT The identification of PTK2B (also known as Pyk2) is interesting. In our P301L tau mutant pR5 mice, GSK3-Tyr279/216 and AT100-positive neurons selectively display a phosphotyrosine-epitope that is associated with an early activation of Pyk2, suggesting ...

Jürgen Götz on The hallmarks of aging.

COMMENT This is a very comprehensive overview with a nice set of figures/tables integrating the contents. j.goetz 0 ...

Jürgen Götz on Formaldehyde induces hyperphosphorylation and polymerization of Tau protein both in vitro and in vivo.

COMMENT Interesting finding. j.goetz 0 ...