Research presented at this year’s AAIC reflected an influx of new money into the field and, with it, a growing diversity of topics. There was new interest in government policy, NIA funding priorities, and underrepresented minorities, along with an even greater emphasis on lifestyle factors and technologies to lessen the impact of a dementia epidemic forecast by demographic change. No large clinical trials presented major data, while a session picking over the ruins of recent BACE inhibitor trials showcased some transparency and shared willingness among pharma companies to learn from failure. Genetics posted news, as did biomarkers, especially blood tests, and much effort being poured into preparing observational cohorts for prevention trials was evident. Imaging continues to light up the field, debuting a new amyloid staging system and offering head-to-head comparisons of tau ligands. Specific tracers for neuroinflammation and other proteinopathies are still out of reach.
Longitudinal data identifies four stages of amyloid plaque buildup, with the earliest deposits appearing in the precuneus and posterior cingulate.
Middle-aged people who exercise more are less likely to become amyloid-positive. In late life, people with brain amyloid who exercise declined more slowly and had less brain shrinkage over the following years.
At AAIC, researchers presented baseline data from an ongoing, five-year study asking whether the anti-Aβ antibody crenezumab can forestall cognitive decline in autosomal-dominant Alzheimer’s disease.
In 2,144 Colombian ADAD family members, plasma NfL in gene carriers rises as early as two decades before their symptoms start.
ApoE2 homozygotes have a dramatically lower risk of AD than even the previously known low-risk E2/3 heterozygotes. More study of this protective allele could reveal roots of resilience.
New genes linked to early and late-onset AD offer up mechanistic insight, potential targets for treatment.
At AAIC, researchers touted phospho-tau species, especially p217 and p181. They tick up in CSF as an early response to amyloid accumulation.
At this year’s AAIC, no sooner had scientists reported that phospho-tau in the CSF might reflect early responses to amyloid, than they reported parallel data for phospho-tau in blood.
A plasma assay for Alzheimer’s could radically speed up screening for clinical trials; alas, competing assays don’t measure the same thing.
What’s with all those head-to-head comparison studies of academic and commercial biomarker tests? Could we not just pick one that works, and be done?
Protein levels track with cognitive function and can distinguish Alzheimer’s patients from controls.
Changes in the composition of the cerebrospinal fluid and synapses may reveal novel insights into AD pathology.
Smartphones and gamified apps move cognitive testing from the lab into the real world. But keeping people engaged remains a problem. Is passive monitoring the answer?
Passive monitoring of old people in their everyday lives is starting to generate new indicators for cognitive impairment.
In patient-derived neurons, tau mutations scupper lysosomes and SORLA shunts APP through different types of endosomes.