Jürgen Götz on Alzheimer amyloid-β oligomer bound to postsynaptic prion protein activates Fyn to impair neurons.

COMMENT Of all Src kinases, Fyn is assuming a critical role in mediating Aβ toxicity. In this Nature Neuroscience paper, Stephen Strittmatter and colleagues show that oligomeric forms of Aβ bind to PrPC, a protein on the extracellular side of the membrane, and th

Jürgen Götz on Calpain Inhibitor A-705253 Mitigates Alzheimer's Disease-Like Pathology and Cognitive Decline in Aged 3xTgAD Mice.

COMMENT Nice paper revealing multiple effects of calpain inhibition! 0 j.goetz

Jürgen Götz on Neuronal mRNAs travel singly into dendrites.

COMMENT This is an interesting paper with implications for local dendritic protein translation in memory formation. 0 j.goetz

Jürgen Götz on Pinning Down Role for Tau Proline Isomers in Alzheimer’s

COMMENT The cis/trans configuration of tau adds another layer of complexity to the changes tau undergoes in diseases such as AD, but first of all, this study underlines that it is the serine/threonine-specific hyperphosphorylation of tau rather than any other mod

Jürgen Götz on Extracting β-amyloid from Alzheimer's disease.

COMMENT Nice review of the original article by Sehgal et al. published in PNAS. Randy Bateman's study in Science on the impaired clearance of Aβ in AD supports the approach. 0 j.goetz Withania somnifera reverses Alzheimer's disease pathology by enhancin

Jürgen Götz on Atomic identification of fluorescent Q-dots on tau-positive fibrils in 3D-reconstructed pick bodies.

COMMENT Excellent approach by Uematsu and colleagues to visualize proteinaceous inclusions at the light- and electron microscopic level in parallel. 0 j.goetz

Jürgen Götz on Using intramolecular disulfide bonds in tau protein to deduce structural features of aggregation-resistant conformations.

COMMENT This is an interesting paper. However, 3R-tau, which has only one cysteine, is not mentioned at all, and in AD, both 4R and 3R tau form aggregates. It might be interesting in subsequent studies to include a 3R truncated form similar to the K18 construct.

Jürgen Götz on In vivo microdialysis reveals age-dependent decrease of brain interstitial fluid tau levels in P301S human tau transgenic mice.

COMMENT Dave Holtzman and colleagues have been using the very elegant method of microdialysis, which allowed them to collect ISF (interstitial fluid) from both wild-type and P301L tau transgenic mice, and to infuse tau aggregates. The paper by Yamada et al. furth

Jürgen Götz on Observations in APP bitransgenic mice suggest that diffuse and compact plaques form via independent processes in Alzheimer's disease.

COMMENT That compact and diffuse plaques develop by independent mechanisms has been suggested in the first paper describing APPsw mutant APP23 mice: These mice develop almost exclusively compact plaques, whereas APP22 mice expressing APPsw together with V717I exp

Jürgen Götz on Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial.

COMMENT This work in humans is nicely supported by studies performed in mice by a Japanese team earlier this year (incidentally, published in the same journal). The mouse work showed that vitamin B deficiency caused cognitive impairment, which could be blocked wi

Jürgen Götz on Neurotoxicity of Alzheimer's disease Aβ peptides is induced by small changes in the Aβ42 to Aβ40 ratio.

COMMENT An enlightening publication combining biophysical and electrophysiological methods with important implications for a treatment strategy. 0 j.goetz

Jürgen Götz on The Plot Thickens: The Complicated Relationship of Tau and Aβ

COMMENT While Aβ and tau exert separate modes of toxicity, it is fascinating to see how more and more details are revealed about how these toxic entities interact to impair neuronal functions in dementias. The new data presented by Lennart Mucke’s team in Science

Jürgen Götz on The Alzheimer's disease mitochondrial cascade hypothesis.

COMMENT A link among mitochondrial dysfunction, tau, and Aβ has also been established in transgenic mice by combining quantitative proteomics with functional assays. 0 j.goetz Amyloid-beta and tau synergistically impair the oxidative phosphorylation system in tri

Jürgen Götz on Caspase activation precedes and leads to tangles.

COMMENT Hyman and colleagues use a powerful in vivo multiphoton imaging approach through craniotomy to monitor the sequence of tau pathology in the inducible tau transgenic mouse model Tg4510, and in mice intracranially injected with tau-expressing AAV (adeno-ass

Jürgen Götz on Drosophila models of human tauopathies indicate that Tau protein toxicity in vivo is mediated by soluble cytosolic phosphorylated forms of the protein.

COMMENT Another piece of evidence that elevated phospho-tau levels, in the absence of tau aggregation, causes toxicity. This fits with our publications referenced below. 0 j.goetz Parkinsonism and impaired axonal transport in a mouse model of frontotemporal demen