… And a Response
Dennis Selkoe replies to Scott Small.
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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.
‘Proteogenomics’ Ties Genes That Control 38 Proteins to Alzheimer’s
Study correlated AD genome-wide association with concentrations of 6,000 CSF proteins to find potential disease variants.
In Alzheimer’s Due to Down’s, Spatial Omics Spots Signs of Trouble
In plaque- and tangle-laden layers of the Down’s syndrome neocortex, neuroinflammation raged, and glia sent death signals to neurons.
Do CSF and Plasma NfL Diverge After Alzheimer’s Disease Onset?
After symptoms of autosomal-dominant AD start, the uptick in neurofilament light chain accelerates in CSF but tapers in plasma.
Is It Time to Approve Drugs Based on Amyloid Removal?
Opinion leaders argue that the field’s knowledge base is now strong enough for regulators to greenlight amyloid-removing immunotherapies without evidence on cognitive/clinical outcomes.
Astrocytes Mount Complex Responses to AD. They Change Over Time
Single-nuclei RNA-Seq of 600,000 astrocytes defined seven subtypes. One revs up metabolic support late in Alzheimer’s disease, before flagging at its end stage.
Receptors and Broken Lysosomes Explain Risk from APOE Variants
ApoE4 transports toxic lipids into lysosomes. ApoE2 and Christchurch variants do not.
'Presymptomatic AD' or 'Asymptomatic at Risk'? Dx Criteria Disagree
Alzheimer’s Association diagnostic criteria favor the former term, International Working Group the latter, for cognitively healthy people with AD biomarkers.
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