The signature fall of cerebrospinal fluid concentrations of Aβ that herald Alzheimer’s may be preceded by a brief boost.
A new screening method detects interactions with mutated proteins that cause neurodegenerative disease.
Two large studies measured the occurrence of amyloid pathology in people with AD and other dementias. They confirm that amyloid may precede dementia onset by more than two decades, and rises with age, particularly in people with the ApoE4 gene.
Like other drug hopefuls for neurodegenerative disease, methylene blue staves off behavioral problems in transgenic mice only if given before memory begins to falter.
Using a viral vector, researchers created mice that express C9ORF72 hexanucleotide repeats in the brain.
In ALS motor neurons, antisense RNA foci outnumber the sense version, and correlate with a marker of pathology.
Denali Therapeutics gets off the ground with one of the largest Series A rounds ever.
Repeated activation of the perforant pathway over five months doubled the area of amyloid plaques in transgenic mice.
A climb in CSF concentrations of Aβ40 and Aβ42 happens just as the first plaques seed the brain in three AD mouse models, according to a new study. Then, as plaques take hold, CSF concentrations dwindle. The initial blip in Aβ has been observed in humans as well, and researchers think it could signify a very early stage of the disease. However, using this as a predictive biomarker could prove tricky, as concentrations on the way up equal those on the way down.
Mutations that cause neurodegenerative disease have numerous effects on cells, but how can scientists track them down? A novel screen reveals that mutant and wild-type versions of five disease proteins differentially bind to dozens of other partners. The mutant proteins cause familial forms of Alzheimer’s, Parkinson’s, Huntington’s, and spinocerebellar ataxia. Their differential interactions may provide clues to disease mechanisms. For example, APPSwe preferentially bound LRPPRC, a protein that regulates mitochondrial genes.
Two meta-analyses offered up the most definitive data to date on the prevalence of amyloid in people without dementia, or with Alzheimer’s or another dementia. As judged by amyloid-PET scans or CSF Aβ42 levels, people with normal cognition are more likely to harbor amyloid as they get older, and the prevalence more than doubled in people carrying the ApoE4 gene. This confirms previous studies. Amyloid prevalence decreased with very old age in people clinically diagnosed with AD, hinting that other age-related pathologies are at play in old people. Those with most non-AD dementias had increasing rates of amyloid with age. The findings may help clinicians choose inclusion criteria for clinical trials, and improve diagnosis.
Integrating data from hundreds of prior studies, computational modeling could change the landscape of AD clinical trial design and finally give the field an overarching description of Alzheimer’s disease. Eli Lilly’s Richard Mohs, CAMD’s Klaus Romero, USC’s Lon Schneider, and Merck’s Julie Stone discussed how modelling works during our last webinar. The full recording, slides, and a Q&A with the panelists are now available on the Webinar background page.
Activated neurons secrete Aβ, but does this lead to more plaques? A new study suggests as much. Researchers in Japan developed one of the first Alzheimer’s mouse models driven by optogenetics. Using light, they turned on a classic hippocampal neural circuit in transgenic mice overexpressing amyloid precursor protein. Five months of chronic stimulation doubled the area of plaques. The results tie overactive neurons to Alzheimer’s pathology and demonstrate the power of this emerging technique.
- Brian Freibaum on Antisense RNA from C9ORF72 Repeats Is Likely Culprit in Patient Neurons
- Ronald Klein on First C9ORF72 Mice Mimic Key Pathology, Behavior
- David Holtzman on Meta-Analyses Deliver Most Definitive Data Yet on Amyloid Prevalence
- Michael Weiner on Meta-Analyses Deliver Most Definitive Data Yet on Amyloid Prevalence
- Akiyama Haruhito on Preventive methylene blue treatment preserves cognition in mice expressing full-length pro-aggregant human Tau.
- M. Flint Beal on Preventive methylene blue treatment preserves cognition in mice expressing full-length pro-aggregant human Tau.
- Markus Otto on Preventive methylene blue treatment preserves cognition in mice expressing full-length pro-aggregant human Tau.