APP Upp: Mutation Nixes Six Amino Acids from Aβ, Spurs Aggregation
Presented at AD/PD, the discovery by scientists in Uppsala is the first APP deletion found to cause Alzheimer’s disease. The same group found the Swedish and Arctic APP mutations.
NEWS
Electrode Detects Aβ Aggregates in Alzheimer’s Plasma
The method purportedly distinguishes patients from controls with more than 90 percent sensitivity and specificity.
Expression, Expression, Expression—Time to Get on Board with eQTLs
A tool of modern genetics, expression studies link GWAS hits to specific cell types, providing clues to pathogenesis. Microglia come up again and again.
At AD/PD Conference, New Alzheimer’s Genes Reinforce Known Pathways
After years of grunt work on next-gen sequencing and expression analysis, geneticists are finally reaping results. The new genes underscore the role of known pathways and cell types in disease.
Amid Brexhaustion, U.K. DRI Marches On, Seeks Innovation Director
Institute to chart new translational research territory.
In Football Players With Possible CTE, Tau-PET Reveals Subtle Tau Deposition
Flortaucipir in former NFL players cropped up in regions known to be affected by chronic traumatic encephalopathy, but uptake was low compared with AD. Whether this reflects low tau deposition or poor tracer binding remain to be seen.
Familial Alzheimer’s Mutations: Different Mechanisms, Same End Result
A fleet of patient-derived neurons show that while an APP mutation shifts where γ-secretase takes its first bite, PS1 mutations blunt the enzyme’s second cut. Eventually, all mutations drive up the Aβ42:40 ratio.
Closing the Book on NSAIDs for Alzheimer’s Prevention
The latest effort to determine if a non-steroidal anti-inflammatory drug protects against Alzheimer’s posted negative results. Time to abandon the approach?
Virtual Exhibit Hall
Alzforum encourages users to visit the Virtual Exhibit Hall, where companies showcase their newest initiatives, products, and services. We welcome Dash Genomics, Inc. and Abcam, which join our other exhibitors — Biogen, BioLegend, BrainXell, NanoString Technologies, and the Jackson Laboratory.
SPOTLIGHT
AD/PD Meeting in Lisbon Hosts a Humbled Field
Held in romantically beautiful Lisbon, the 14th AD/PD conference was the biggest thus far, drawing 3,982 attendees from 73 countries, according to Abraham Fisher, its longtime lead organizer. But as the field grows, it has little to celebrate, and the mood reflected that. Trialists were appealing for patience and pointing to deepening clinical trials skills as they learn from setbacks on investigational therapies, most recently of lanabecestat, crenezumab, and aducanumab. Trials targeting tau were not yet reading out, but the medical food Souvenaid posted modestly positive results. At the other end of the bench-to-bedside spectrum, basic science is diversifying. Next-gen genetics is spilling out gene variants which, together with RNAseq, are energizing research into glial and lipid biology. Debate about the amyloid hypothesis, a fixture at AD/PD, evolved toward a focus on genetic variability in how a person’s innate immune system responds to amyloid deposition. Ab itself? Nothing special about it. It aggregates into an irritant as the brain’s ability to degrade it wanes with age. It starts things off, but other factors later dominate the disease. Or so researchers now think. Read Madolyn Rogers and Gabrielle Strobel’s coverage.
Closing the Book on NSAIDs for Alzheimer’s Prevention
Ever since epidemiological studies found that people who take non-steroidal anti-inflammatory medications have lower rates of developing Alzheimer’s, researchers have tried turning this association into treatment success. It never worked. Now, in a clinical trial, the NSAID naproxen did not delay cognitive decline in people in their 60s who were at high risk of Alzheimer’s, but it did cause significant side effects. Together with past trials, the new results suggest that NSAIDs cannot prevent AD.
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