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.
NEWS
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.
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.
Inactivity May Be a Symptom, Not a Cause, of Dementia
People who report not participating in social or cognitive activities are more likely to develop dementia within the next few years, but not after that. The findings cast nonparticipation as a consequence, not a cause, of neurodegeneration.
Striking Microgliosis in New APP Knock-in Mice
Plaques abound, cytokines spike, microglia swell with lipids and send out spermine SOS signals in Denali model. Mice will be shared, allowing unrestricted use.
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
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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