Tau in the plasma rises after traumatic brain injury, with cognitive decline, and progression to mild cognitive impairment.
ApoE, especially E4, interacts directly and indirectly with tau. This worsens outcomes along the pathogenic process, from soluble tau to glial activation and brain atrophy. All without Aβ.
A birth cohort study in New York City finds a sharp drop in dementia incidence in people born after 1929. Neither better cardiovascular health nor more education explain the data.
Autophagy spares motor neurons from synaptic ruin early in disease, but stokes the fires of neuroinflammation later on.
Engineering mice to express a tagged polyA-binding protein in specific cell types allows researchers to pull out neuronal, astroglial, or microglial mRNAs from the intact brain and examine each cell type′s mix of mRNA 3' ends.
RIPK1 catapults microglia into an inflammatory frenzy, disrupting their lysosomal pathway and undermining Aβ clearance. A new drug target?
Two new mouse studies show that a ketogenic diet that avoids obesity improves the health of mind and body, increasing median lifespan. Related studies hint at possible benefits for Alzheimer’s disease.
CryoEM reveals high-resolution view of full length of Aβ42 in a novel conformation.
Despite being identified as an Alzheimer’s risk factor as far back as 1993, ApoE has not given rise to new therapeutics. Might that change with a new report that characterizes ApoE’s effect on tau? The study claims that, starting with accumulation of soluble tau, the presence of ApoE, especially its E4 version, exacerbates every major step along the pathogenic cascade. Axonal tau redistribution to neuronal soma, neurodegeneration and atrophy, micro- and astroglial activation—for all those measures, lack of ApoE was strangely protective, ApoE was bad, ApoE4 worst. ApoE carriers with non-Aβ tauopathies had more regional neurodegeneration, and E4 homozygote people with mild AD progressed faster.
In Alzheimer’s disease, microglia change from Aβ-eating machines into cells without much of an appetite. What causes this shift? One suspect is the RIPK1 kinase, which microglia express in response to inflammatory signals. According to new research, RIPK1 stalls Aβ breakdown by crippling the lysosomal machinery, and blocking the enzyme reduces plaques in AD model mice and improves their memory. The results point to a possible new treatment target for Alzheimer’s and related disorders. More broadly, the study characterizes RIPK1-dependent pathways in microglia.
Two independent studies report that a high-fat, low-carb regimen, known as the ketogenic diet, preserves memory and physical fitness in old mice. The diet also nudged up median lifespan, upping PPARα signaling and reducing mTOR signaling, changes previously tied to lifespan extension. Could this unpalatable diet, or supplements that boost ketone bodies, help people with Alzheimer’s?
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