Does Tangle Progression Follow ApoE Expression?
Correlating PET imaging with spatial transcriptomics revealed paths for the progression of tau pathology throughout the brain.
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Behold, Plaques Mapped in Whole Brain at High Resolution
Advances in microscopy yield unprecedented views of Aβ plaques in vivo and ex vivo. The vistas offer new insights about how plaques form, grow, and clear.
Receptor Decoy Raises Risk of Alzheimer’s—But Only in Women
High sST2, an IL-33 receptor fragment, raises the odds of Alzheimer’s in women who carry APOE4. A variant that lowers sST2 mobilizes microglia, protects against AD.
Sylvain Lesné, Who Found Aβ*56, Accused of Image Manipulation
Other scientists found indications of potentially doctored western blots in multiple papers, including several on Aβ*56. Investigations are underway at journals, NIH, UMinnesota.
Don’t Name It: Glial States Confound Easy Labels
By consensus, leaders in the astrocyte and microglia fields recommend that investigators eschew names in favor of detailed descriptions of reactive glia, with a focus on functional changes.
In Parkinson’s, Synuclein Fibrils Fold Differently Than in MSA
Synuclein fibrils from Parkinson’s disease, PD dementia, and dementia with Lewy bodies share the same protofilament structure. MSA fibrils are different.
Mesh, not Membrane: Pia Filters CSF, Gets Clogged by Aβ Fibrils
New data show the pia is a permeable mesh that filters CSF and harbors macrophages. It thins with age but thickens in a mouse model of amyloidosis.
Do a Few “Master” Sites Control Tau Hyperphosphorylation?
Phospho groups at key residues, such as threonine 181, promoted phosphorylation at multiple distant sites along the protein, suggesting a regulatory role.
In the U.S., 40 Percent of All-Cause Dementia Is Preventable
Obesity, hypertension, and physical inactivity account for one in five cases.
In Down's Syndrome, Blood P-Tau217 Detects Plaques and Tangles
In young adults with Down’s, plasma phospho-tau217 correlated with amyloid and tau PET positivity. With great accuracy.
Too Clingy: Extra Hydrogen Bond Prompts Protein Aggregation
Certain mutations in TDP-43, tau, and NfL add one hydrogen bond to their low-complexity domains. This warps phase transition and strengthens self-aggregation.
CAPturing Oligomers from Biofluids
With its affinity for β-sheets, a probe called Capture Molecule for Amyloid Precipitation, aka CAP-1, pulls α-synuclein and other soluble amyloids out of solution.
Lecanemab: FDA Set Accelerated Approval Decision for January 2023
The agency accepted Eisai and Biogen’s application for priority review under the accelerated approval pathway, based on Phase 2 biomarker data.
A Putrid Problem: Astrocytic Urea Cycle in Alzheimer’s?
In astrocytes, Aβ revs up urea metabolism, spitting out the intermediate putrescine. This gets turned into the neurotransmitter GABA, which blunts synaptic transmission and memory in mice.
Astrocyte-to-Neuron Conversion Questioned
A spate of recent studies could not replicate the finding that knocking down the RNA-binding protein PTBP1 in astrocytes triggers their conversion to neurons. Leaky expression of the knockdown construct in endogenous neurons may be to blame.
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