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.
NEWS
Alzheimer’s Field Loses Fred van Leeuwen, 71
Van Leeuwen was best known for finding frameshift mutations in APP and ubiquitin B in the brains of people with tauopathies.
Massive GWAS Meta-Analysis Digs Up Trove of Alzheimer’s Genes
Researchers unearthed 75 risk loci, 42 of them new, and nominated candidate genes for each. A polygenic risk score based on all variants predicted AD risk with high accuracy.
TWAS x GWAS? Transcriptome Analysis Finds 11 Parkinson’s Genes
Transcriptomic and epigenomic data pin PD risk genes in GWAS loci; six affect splicing, five expression, four are new.
Earliest of Them All: Blood P-Tau231 Assay Flags Pre-Amyloid Alzheimer’s
The first ultrasensitive plasma test for this old marker differentiates Alzheimer’s from healthy controls and non-AD dementias. It segregates people stepwise at phases of pathogenesis down to Braak stages 1 and 2 and below amyloid PET positivity.
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.
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.
New Smartwatch Utility Tracks Parkinson’s Symptoms
Sensor algorithms can accurately capture patterns of resting tremor and dyskinesia. This could help clinicians manage symptoms and medication.
Virtual Exhibit Hall
Alzforum encourages users to visit the Virtual Exhibit Hall, where companies showcase their newest initiatives, products, and services. We welcome F. Hoffmann-La Roche, joining our other exhibitors — Biogen, BioLegend, Abcam, BrainXell, and the Jackson Laboratory.
SPOTLIGHT
Would ApoE Make a Better Therapeutic Target Than A?
Antibodies such as aducanumab clear amyloid plaque from the brain, but they also cause tiny tears in cerebral blood vessels that cause ARIA. Is there a safer way? In mice, antibodies directed against ApoE, a component of dense-core plaques, mopped up deposits in brain and blood vessels more effectively than did aducanumab. Importantly, this therapy caused no microhemorrhages. The data hint that antibodies targeting ApoE could be safer for long-term therapy.
Massive GWAS Meta-Analysis Digs Up Trove of Alzheimer’s Genes
Want more Alzheimer’s genes? A new GWAS meta-analysis has you covered, turning up 42 new loci linked to the disease. Leading candidate genes participate in amyloid and tau metabolism, endocytosis, and immunity, highlighting the importance of these processes in disease pathogenesis. Piled into a polygenic risk score, they predict risk of dementia in healthy controls with 84 percent accuracy. A second study maps DNA to identify functional genes at many AD loci. Get the lowdown in Madolyn Rogers’ story.
TWAS x GWAS? Transcriptome Analysis Finds 11 Parkinson’s Genes
Transcriptomic and epigenomic data separated GWAS wheat from chaff, uncovering 11 Parkinson’s risk genes. Five regulate gene expression, six dictate alternative splicing. Four are new to PD. Most genes are highly expressed in glial cells, not neurons. Which pathway predominated? You guessed it: lysosomal degradation.
Earliest of Them All: Blood P-Tau231 Assay Flags Pre-Amyloid Alzheimer’s
The first ultrasensitive plasma p-tau231 assay cleanly differentiated Alzheimer’s disease from healthy people and from those with other neurodegenerative disorders. It also segregated different phases of AD progression and picked up preclinical pathology earlier than p-tau181 and Aβ PET. P-tau23 is the only blood marker so far to show change prior to Braak stage III. It correlated with CSF p-tau231, tau PET as measured with the MK-6240 tracer, and plaque burden as measured with the AZD4694 tracer, showing that it fits in with established markers of AD pathogenesis. The data suggests that p-tau231 can more crisply define normal aging and may be the earliest specific blood biomarker of AD pathology known thus far.
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