Held in romantically beautiful Lisbon, this AD/PD 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 continuing 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. Aβ 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.
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.
A tool of modern genetics, expression studies link GWAS hits to specific cell types, providing clues to pathogenesis. Microglia come up again and again.
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.
Scientists at AD/PD 2019 see a Goldilocks of microglial activation: Both too little and too much is bad in an injured brain. How could a therapy make it just right?
Inhibiting the receptor activates microglia to mop up debris, making CD33 an attractive therapeutic target.
Speakers at AD/PD 2019 reported that AD risk factors mess up lipid metabolism in glial cells. In cellular models, speeding the clearance of fats lessened pathology.
By slipping human microglia inside the mouse brain, researchers hope to better monitor their response to pathologies, such as Aβ.
Scientists are probing saliva and skin secretions for telltale signs of Parkinson’s disease. Their prize? A diagnostic test at the pre-motor stage.
Scientists know that the retina changes in people with preclinical AD; alas, there is neither consensus nor convergence in the field of retinal imaging. An upcoming initiative aims to determine which measures are most robust.
Microglia cleanup, mitophagy, axonal plasticity, blood-brain barrier. A renewed focus on ApoE4 is revealing new ways in which this isoform renders the brain vulnerable to Alzheimer’s.
By aging cultured neurons and manipulating them to stimulate endocytosis or interfere with vesicle release, researchers can bring about characteristics of Alzheimer’s—without adding APP or Aβ.
As data increasingly blame the microglia response as a driving force in Alzheimer’s disease, researchers are investigating whether tempering these cells will aid cognition.
At AD/PD 2019, scientists implicated both peripheral and central innate immunity in promoting propagation.
An electron microscopy study reveals a jumbled mess of membrane chunks and malfunctioning organelles, bound together by phosphorylated or truncated α-synuclein.
“We are learning” was the tenor of debate about the latest round of setbacks for anti-amyloid trials in symptomatic Alzheimer’s disease at a recent conference in Lisbon.
Lanabecestat, elenbecestat, and umibecestat all showed data at the AD/PD conference in Lisbon. Learn what definitely doesn’t work and what might yet.