Single-Cell Expression Atlas Charts Changes in Alzheimer’s Entorhinal Cortex
Specific patterns of expression defined distinct subtypes of neurons, astrocytes, oligodendrocytes, and microglia in this early affected brain region.
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Cell-Specific Enhancer Atlas Centers AD Risk in Microglia. Again.
Cataloguing enhancer-promoter interactions in the four major cell types of the brain, researchers found that Alzheimer’s risk variants predominantly appeared in microglial enhancers.
AD Genetic Risk Tied to Changes in Microglial Gene Expression
Functional variants of AD GWAS hits found in enhancers of myeloid genes.
Next-Generation Tau PET Tracers Strut Their Stuff
Emerging data on new tau ligands raise hope of more signal, less noise, and help with a broad range of tauopathies. Read news culled from the AD/PD and HAI 2017 meetings.
Absent Aβ, Blood-Brain Barrier Breakdown Predicts Cognitive Impairment
A leaky blood-brain barrier in the hippocampus correlated with cognitive impairment, independently of other vascular risk factors or Alzheimer’s pathology.
Islands of Mutated Neurons Dot the Brain. Are They Bad for Us?
Clusters of neurons harboring somatic mutations in 56 genes linked to neurodegenerative diseases may be commonplace in the human brain.
Mutations in Epigenetic Gene Linked to Neurodegeneration
Loss-of-function variants in the demethylase TET2 raise a person’s risk for early and late-onset Alzheimer’s, as well as FTD and ALS, suggesting a common mechanism.
GnomAD: Stunning Variation Seen in Largest Collection of Human Genomes
In seven papers, researchers presented a dazzling set of findings gleaned from 125,748 exomes and 15,708 genomes housed in a new database. Tidbits emerge on tau, LRRK2, and other proteins implicated in neurodegeneration.
Conformers Confirmed: Structure of Pick’s Tau Distinct from AD Tau
A molecular-level view of tau filaments from a person with Pick’s disease reveals that the protein folds up differently than it does in Alzheimer’s disease.
Blood-Brain Barrier Surprise: Proteins Flood into Young Brain
As mice age, a busy receptor-mediated protein transport across the barrier wanes; inhibiting an alkaline phosphatase restores it. Meanwhile, the aging barrier becomes generally leaky to large molecules.
γ-Secretase Spotted Traveling Solo or in Pairs, Not in Big Groups
Behold single proteins on the move: Super-resolution microscopy of living cells suggests the infamous protease does not form complexes with other secretases in the plasma membrane—in mouse fibroblasts, that is.
FDA OKs Cognition as Sole Outcome Measure for Preclinical AD Trials
The agency is accepting comments on a draft guidance that updates its recommendations for early AD trials, as well as on its first-ever guidance for ALS drug development.
Single-nucleus RNA Sequencing Misses Activation of Human Microglia
Technical limitations may have misrepresented the transcriptional state of these cells, obscuring detection of their activation signature in frozen postmortem tissue from Alzheimer’s brain.
Alzheimer’s Gene BIN1 Promotes Synaptic Transmission
In a conditional mouse knockout, lack of neuronal BIN1 slowed excitatory signaling, leading to spatial memory problems. Could this play a role in Alzheimer’s?
Paper Alert: Trafficking Variants Cause BACE Buildup in Axons
In mice lacking the recycling protein GGA3, BACE1 trafficking stalls, local Aβ production increases, and axons swell. Does this explain the neuritic dystrophies seen in early AD?
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