Women and Men Differ in Their Genetic Risk for Alzheimer’s Progression
Sex-specific polygenic hazard scores predict pathology and cognitive decline.
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Does Huntington’s Disease Begin in the Womb?
Tissue from 13-week-old fetuses carrying the huntingtin repeat expansion shows defects in neuronal polarity and proliferation, which lead to fewer neurons populating some brain regions.
Can an Antibody Allele Boost Your Alzheimer’s Risk By Giving Herpes an Edge?
Homozygous carriers of GM17—a common IgG1 variant the HSV-1 virus has evolved to evade—had quadruple the risk of developing AD. In a small Swedish cohort, that is.
Protective AD Variant Pinpoints Sweet Spot for Microglial Activation
Phospholipase C-γ2 acts downstream of TREM2 to rev up beneficial inflammation, phagocytosis, and cell survival.
New ACE Variant Speeds Neurodegeneration in Alzheimer’s Mice
The R1279Q variant of angiotensin-converting enzyme associates with AD and causes neurodegeneration in mice. In a model of amyloidosis, it accelerates decline.
Can Muscle Macrophages Coax Spinal Cord Microglia to Protect Neurons?
In a mouse model of ALS, removing mutant SOD1 from peripheral myeloid cells relieved neuroinflammation and extended lifespan.
Plasma Aβ Test Wins Approval—Are p-Tau Tests Far Behind?
Regulators in the U.S. and Europe have certified a mass-spectrometry-based blood test for amyloid-β. Plasma phospho-tau markers are poised to come next.
Epoxide Hydrolase, a Fat New Target for Alzheimer’s Therapy?
The enzyme degrades anti-inflammatory fatty acids in the brain. Blocking it with a brain-penetrant small molecule calmed A1 astrocytes, synapse-eating microglia, and improved amyloidosis and cognition in a mouse model.
New Data Question Anti-Microbial Powers of Aβ
Plaque-ridden 5xFAD mice were no better at fending off an intracerebral herpes virus infection than their wild-type counterparts. The virus was not to be found within Aβ plaques and did not spur plaques to form.
PWAS x GWAS? Proteome Analysis Nets 10 New Alzheimer’s Genes
By comparing protein changes with GWAS data, scientists identified new links to AD. This method can unearth genes that otherwise fall short of genome-wide significance.
Make Proteins, Save Memory: The Cellular Stress Response and Synapses
In mouse models of Aβ toxicity and amyloidosis, inhibiting the integrated stress response restored protein production, spared synapses, and brought back memory.
Not Merely Tau Tombstones, Neurofibrillary Tangles Are Dynamic
In mouse brain slices at least, tau shuffles in and out of protein inclusions. The tangles grew more inert as the tissue aged.
In Triculture Model, Astrocyte-Microglia Cross Talk Spurs Inflammation
When cultured with human neurons expressing a familial Alzheimer’s gene, both microglia and astrocytes were necessary to spike complement C3 and send inflammation into overdrive.
Would ApoE Make a Better Therapeutic Target Than Aβ?
In mice, an anti-ApoE antibody removed plaques from the brain’s parenchyma and blood vessels better than aducanumab. Importantly, it caused no microhemorrhages.
Cognition in Aging Women: From Higher Perch, a Steeper Fall
Based on pooled data from five well-characterized cohorts, women appear to initially outperform men, but then slide faster, on global cognition and executive function. Oddly, this was not true for memory.
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