… And a Response
Dennis Selkoe replies to Scott Small.
NEWS
An Open Letter to Dennis J. Selkoe, M.D.
Scott Small reacts to a recent perspective paper and the discussion it engendered.
Sans Presenilin-2, Lysosomes Struggle. Synapses, Memory Circuits Erode
In mice, crippling PSEN2 worsened amyloid deposition, synaptic dysfunction, and deficit in working memory.
Can Anna Karenina Help Scientists Find Proteins That Cause Alzheimer’s?
A Tolstoy-inspired method identifies AD variants that exert similar effects, pinpointing causal AD proteins—six known, plus a new one, RET.
SIRT6 Reported to Destabilize APP
As levels of the deacetylase wane with age, more APP gets processed in endosomes, worsening amyloid pathology.
RAND Urges Free Cognitive Testing
Report probes predictors of dementia, the benefits of early detection, and people’s motivation to seek testing and treatment.
‘MGWAS’ Ties Brain Metabolites to Alzheimer’s, Parkinson’s, More
Lipids, amino acids, carbohydrates, and other molecules in the CNS linked to genetic variants, some of which upped the risk for neurodegenerative disease.
Is Your Brain Aging Fast? Plasma Proteins Might Tell
Eight proteins in blood associate with faster brain aging, five with slower. The extracellular matrix protein brevican comes with larger cortical volume, lower dementia odds.
SPOTLIGHT
Sans Presenilin-2, Lysosomes Struggle. Synapses and Memory Circuits Erode
As a catalytic subunit of γ-secretase, presenilin 2 churns out Aβ peptides from its perch within lysosomes. A new study reports that in mice, either mutating PSEN2, or deleting it entirely, has the same effect: endolysosomes back up, hippocampal circuits weaken, and working memory falters. Both scenarios also promote amyloidosis.
Dear FDA: Is it Time to OK Drugs Based on Amyloid Removal?
Catch up on the latest contributions to a debate about approving immunotherapies based on robust biomarker change, without cognitive/clinical outcomes. This past week, clinician-researchers weighed in from South Korea, where lecanemab is approved, as did a statistician formerly at the FDA. U.S.-based critics elaborated on their disagreement and called on drug sponsors to share data correlating degree of amyloid reduction with clinical outcomes. This discussion remains open. Peruse the proposal, the 23 views articulated so far, then share your own.
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