CONFERENCE COVERAGE SERIES
Alzheimer's Association International Conference (AAIC) 2024
Philadelphia, Pennsylvania and Online
28 July – 01 August 2024
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.
Are Alzheimer’s Blood Tests Ready for Primary Care?
Plasma p-tau217/tau217, alone or with Aβ42/40, identified people with amyloid pathology more accurately than did expert clinical assessment.
Living Among Us: People Whose Alzheimer’s Is Already Being Prevented
On gantenerumab, some people with dominantly inherited AD mutations remain plaque- and tangle-free, and cognitively healthy, years after their expected age of onset.
First Success Stories From Alzheimer’s Secondary Prevention Trial
Case studies from the Dominantly Inherited Alzheimer Network trial show amyloid immunotherapy can prevent tangles and cognitive decline in some mutation carriers.
Liraglutide Trial Was Negative Four Years Ago, Still Negative Today
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.
How Presenilin Mutations Hobble γ-Secretase Predicts Onset, Progression
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.
Two New Deaths on Leqembi Highlight Need to Better Manage ARIA
These are the first deaths reported from clinical use of lecanemab. One was APOE4 homozygote; both developed severe ARIA-E and seizures.
Implicated in ARIA: Perivascular Macrophages and Microglia
These immune cells spew free radicals and inflammatory cytokines that damage blood vessels, contributing to edema and brain bleeds.
I’m Open! Exposed Enhancers Reveal Masters of Microglial Moods
At AAIC, scientists reported how specific enhancer motifs and transcription factors cooperate to shift microglia into myriad reactive states, and back again.
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.
A Plasma Test for Tangles?
In blood, fragments of tau containing the microtubule binding region could help diagnose dementia due to Alzheimer’s disease.
By Setting Standards, Experts Aim to Tame a Wild West of AD Blood Tests
An expert panel has laid out performance standards on amyloid tests. Clinical context will dictate accuracy, and online calculators might help.
In Head-to-Head Testing, P-Tau217/Tau217 Comes Out on Top. By a Hair.
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.
A Finger-Prick Test for Alzheimer’s Disease?
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.
NULISA—A New Proteomic Method to Revamp Biomarker Analysis
Alzheimer’s markers are quantifiable in dried plasma, simplifying future diagnoses. With new ultrasensitive assays, hundreds of proteins could be analyzed this way.
At the Edge of Spatial Omics, Cellular Response to Amyloid Comes into View
At AAIC, scientists linked Alzheimer’s pathology to the demise of nearby neurons, and implicated plaque-adjacent glia in sparking tau pathology.
Is the ‘Atrophy’ of Immunotherapy Just the Dismantling of Plaque ‘Suburbia’?
Plaques and their surrounding cells and neurites occupy 6 percent of cortical volume. Their removal could account for shrinkage during amyloid immunotherapy.
Leqembi: The Case for Long-Term Dosing
At AAIC 2024, speakers pointed to worsening biomarkers and cognition after dosing stopped, and linked the protofibrils targeted by lecanemab to neurodegeneration.
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.
That Retrotransposon in TMEM106b: Friend or Foe?
How—or even if—a newly spotted AluYb8 element raises risk of neurodegenerative disease has become a question of intense interest. Centenarians, it seems, are spared.