Sequences of more than 2,600 Icelanders link loss-of-function mutations in the ABCA7 gene to increased risk for Alzheimer’s.
Antibody against aggregated Aβ reported to clear out amyloid from brain, and perhaps slow cognitive decline, in people with prodromal Alzheimer’s disease.
Researchers found inherited recessive or dominant de novo mutations in people with sporadic ALS whose parents did not have the disease.
Motor neurons may be susceptible to ALS because they lack a chaperone that folds SOD1.
Phase 2 trial data show promise, say researchers.
Cognitively normal people with levels of CSF Aβ42 near the cutoff point associated with amyloid pathology are likely to cross that threshold within three years.
The British government, pharmaceutical companies, and a research charity establish a venture capital fund.
A chloride ion imbalance renders γ-aminobutyric acid (GABA) receptors excitatory.
Researchers in Iceland have just published findings gleaned from the whole-genome sequences of 2,636 of the island’s inhabitants. Combined with genotyping data on thousands more of their countrymen and a thorough genealogical record that goes back hundreds of years, these data have allowed the scientists to infer the incidence of rare gene variants in almost 300,000 people. This data gives unique insights on human genetics and how those variants relate to disease. Looking at genetic variation associated with Alzheimer’s, the researchers found polymorphisms in the ABCA7 gene that reduce levels of the protein and double the risk for the disease. Not only does the study solidify ABCA7’s role in Alzheimer’s, it reveals that lower amounts of the protein are the likely culprit.
Engage target: Check. Who would have thought an interim analysis of an ongoing Phase 1b study could dominate a conference attended by 3,100 researchers, to say nothing of adding billions to a company’s market capitalization? More importantly, the presentation by Jeffrey Sevigny at Biogen at the 12th International Conference on Alzheimer’s and Parkinson’s Diseases, held March 18 to 22 in Nice, France, gave a much-needed shot in the arm to researchers and patients demoralized from a decade of underwhelming clinical trial results. Formerly known as BIIB37, the anti-Aβ antibody aducanumab removed amyloid deposits from the brain of people with prodromal Alzheimer’s in a dose-dependent fashion. The effect was large: At the highest dose, the amyloid appeared to be just about gone. Aducanumab teased with a clinical benefit, though the trial was not powered to show that. ARIA-E occurred in many cases. This raised the question of whether ARIA-E is a sign that the antibody is working and should be managed to avoid harm.
A Phase 2 trial found that the anti-convulsant levetiracetam restored normal activity to neurons in the hippocampus and entorhinal cortex in people with mild cognitive impairment. It also improved their performance on a memory test. A Phase 3 trial is slated to begin later this year.
It is widely believed that excess GABA, a major inhibitory neurotransmitter in the brain, suppresses neural circuits in people with Down's syndrome. New research might stand that theory on its head. Scientists report that in a mouse model of this disease GABA does not inhibit neurons, but excites them. The about-face results from an imbalance in chloride ions. When GABA receptor channels open, the ions flow out of neurons instead of in, making the cells more likely to fire rather than less. An FDA-approved drug that blocks chloride transport improves cognitive deficits in the mice. Could it also treat people?
- Steven Estus on Loss-of-function variants in ABCA7 confer risk of Alzheimer's disease.
- Cheryl Wellington on Loss-of-function variants in ABCA7 confer risk of Alzheimer's disease.
- Brett Garner on Loss-of-function variants in ABCA7 confer risk of Alzheimer's disease.
- Milan Fiala on Cytokine Takes Aβ Off the Menu for Microglia
- Gary Landreth on Cytokine Takes Aβ Off the Menu for Microglia
- Zuzana Siskova on Pathological tau disrupts ongoing network activity.
- John Hardy on Mutant Presenilin Knock-in Mice Mimic Knockouts, Stir Old Debate