Questions, Questions for Donanemab, Lecanemab
As immunotherapies enter care, scientists explore when to stop them, how amyloid removal relates to cognitive benefit, and whether fluid markers will track both plaque and tangles responses.
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As immunotherapies enter care, scientists explore when to stop them, how amyloid removal relates to cognitive benefit, and whether fluid markers will track both plaque and tangles responses.
At AAIC 2024, speakers pointed to worsening biomarkers and cognition after dosing stopped, and linked the protofibrils targeted by lecanemab to neurodegeneration.
Plaques and their surrounding cells and neurites occupy 6 percent of cortical volume. Their removal could account for shrinkage during amyloid immunotherapy.
At AAIC, scientists linked Alzheimer’s pathology to the demise of nearby neurons, and implicated plaque-adjacent glia in sparking tau pathology.
Alzheimer’s markers are quantifiable in dried plasma, simplifying future diagnoses. With new ultrasensitive assays, hundreds of proteins could be analyzed this way.
Markers for AD can be measured in dried blood. This could greatly simplify diagnosis in far-flung areas. With new ultrasensitive assays, hundreds of proteins could be tested this way.
The percentage of tau fragments phosphorylated at amino acid 217 best pegged people with brain amyloid or tangles. The ratio’s edge over other markers is slight, though.
An expert panel has laid out performance standards on amyloid tests. Clinical context will dictate accuracy, and online calculators might help.
In blood, fragments of tau containing the microtubule binding region could help diagnose dementia due to Alzheimer’s disease.
When faced with amyloid, ApoE4 microglia crank up pro-inflammatory genes. ApoE2 microglia do the opposite. They quell neuroinflammation via the vitamin D receptor.
At AAIC, scientists reported how specific enhancer motifs and transcription factors cooperate to shift microglia into myriad reactive states, and back again.
These immune cells spew free radicals and inflammatory cytokines that damage blood vessels, contributing to edema and brain bleeds.
These are the first deaths reported from clinical use of lecanemab. One was APOE4 homozygote; both developed severe ARIA-E and seizures.
A study links 161 PSEN 1 mutations to age of onset and disease progression. Good news for variant calling, and for developing γ-secretase modulators.
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