Microglial Epigenetics Hints at How ApoE Toggles Alzheimer’s Risk
When faced with amyloid, ApoE4 microglia crank up pro-inflammatory genes. ApoE2 microglia do the opposite. They quell neuroinflammation via the vitamin D receptor.
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; both were APOE4 homozygotes who developed severe ARIA-E and seizures.
A study links 161 different PSEN1 mutations to age of symptom onset and Alzheimer’s disease progression. This is good news for variant calling, and for developing therapeutic γ-secretase modulators.
Contrary to media stories, results of a small trial, which finished four years ago, did not demonstrate protection against cognitive decline or against brain shrinkage in people with Alzheimer’s.
Case studies from the Dominantly Inherited Alzheimer Network trial show amyloid immunotherapy can prevent tangles and cognitive decline in some mutation carriers.
On gantenerumab, some people with dominantly inherited AD mutations remain plaque- and tangle-free, and cognitively healthy, years after their expected age of onset.
The Alzheimer’s Association International Conference, held July 28 to August 1, drew 8,200 attendees to the beautiful if distressed city of Philadelphia. Thousands more watched online. The growth reflects expansion in both research topics and commercialization ranging from drugs to mobile testing apps to head-only desktop MRI scanners. The big news? Blood tests are getting really good. Amyloid immunotherapy gained ground with eight-year treatment data in DIAN and three-year treatment data for lecanemab, while regulators around the world are deciding whether to approve. New clinical trial data were sparse but research from human genomics to nodal biology strutted its stuff. Watch this space for stories on these and other topics in the next few weeks.
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