Kenneth Kosik on Might SORL1 Bind Tau in Glia, Fuel Its Aggregation?

COMMENT This paper by J.M. Cooper et al. is a well-executed study that advances our thinking about the route tau travels once internalized. In essence, the problem we face is that, internalized via LRP1 through which it enters endosomes, tau must escape the endos

Kenneth Kosik on APOE Christchurch Variant Tames Tangles and Gliosis in Mice

COMMENT In 2019, Arboleda-Velasquez et al. reported the remarkable case of a woman who harbored the highly penetrant PSEN1-E280A Alzheimer’s mutation, but was spared the disease for 28 years beyond the mean age of onset that occurred in the late 40s of the other

Kenneth Kosik on Field Says Farewell to Neuropathologist Yasuo Ihara, 78

COMMENT Yasuo's death brings a flood of memories from the beginning of our careers when he arrived in the Selkoe lab at McLean Hospital, Belmont, Massachusetts, where I was fresh out of a neurology residency without a clue about how to do research. Yasuo kne

Stella Glasauer, Kenneth Kosik on Human tau mutations in cerebral organoids induce a progressive dyshomeostasis of cholesterol.

COMMENT interest in our paper and their comment. The identifier ACAT has been used ambiguously in the literature:

Kenneth Kosik on Membrane Border Patrol: Cholesterol Stymies Tau Uptake, Aggregation

COMMENT Tuck et al. make an important contribution to the problem of tau uptake as it transits between cells. This problem has become more interesting with the recent publication of many tau cryoEM structures that link specific disease phenotypes to tau conformat

Kenneth Kosik on John Trojanowski, 75, a Giant in the Field of Neuropathology

COMMENT Nothing shakes one’s own sense of mortality more than the death of a contemporary. At a time when Tau was still new and shiny, and every day brought a new insight, a time when many of us were meeting each other for the first time at the starting gate of o

Kenneth Kosik on Stress-Induced Cellular Clearance Is Mediated by the SNARE Protein ykt6 and Disrupted by α-Synuclein.

COMMENT Increasingly, the lysosome is becoming the centerpiece for understanding the cell biology of inclusion body neurodegenerative diseases. The fascinating paper by Cuddy et al. adds an intricate layer of regulation over lysosomal activation in the context of

Kenneth Kosik on Islands of Tau Coat and Protect Cytoskeleton

COMMENT Phase states of tau can regulate microtubule function These new tau papers advance our knowledge of tau protein function at a mechanistic level. Previous work showed that tau is an RNA-binding protein capable of undergoing liquid-liquid phase separation (

Kenneth Kosik on Tau Droplets Sprout Microtubules

COMMENT of California Santa Barbara is the co-author of this comment. kosik 0 Reaction rates for

Kenneth Kosik on More Droplets of Tau

COMMENT comment. kosik 0 RNA stores tau reversibly in complex coacervates. Conformations of intrinsically

Kenneth Kosik on ‘Godfather of Tau’ Skip Binder Dies at 63

COMMENT Irreverent, witty, lively, and always full of kindness and generosity, Skip’s untimely death must give pause to all of us who knew him, and many more who only knew of him. We should build upon his insights as we delve ever more deeply into the diseases th

Kenneth Kosik on NIH Calls for More (and Different) Research on Preventive Measures

COMMENT The NIH State-of-the-Science Conference has set a threshold of evidence required to make recommendations that goes beyond what would best serve the interests of public health. This may seem paradoxical, because as scientists we demand the highest standard

Kenneth Kosik on Phoenix: Trials in Colombia and the U.S. for Those at Highest Risk?

COMMENT The API project is important and valid, but I'd like to point out one oversight in this story. While the two study populations targeted at present are primarily selected on the basis of genetic risk, the non-genetic risk factors for AD, such as cardi

Kenneth Kosik on Deletion of the ubiquitin ligase CHIP leads to the accumulation, but not the aggregation, of both endogenous phospho- and caspase-3-cleaved tau species.

COMMENT This paper by Dickey et al. is a strong addition to mounting evidence that phosphorylated tau is a dangerous moiety. One way the neuron protects itself from this danger is to call upon CHIP, Hsc70, and ubiquitin to modify tau in a manner that may simultan

Kenneth Kosik on A novel method of generating neuronal cell lines from gene-knockout mice to study prion protein membrane orientation.

COMMENT The cell fusion looks really interesting, especially considering (1) the challenge of getting cellular models of AD, (2) the great number of constructs that need analysis, and (3) the otherwise difficult analysis of gene dosage. 0 kosik