Caught amid COVID-19, the organizers of this meeting decided on March 10, 2020, to switch to a virtual format. It offered prerecorded lectures and e-posters, as well as livestreamed discussions, “Meet-the-Professor” audio chats, and a virtual exhibit hall. New data included widely anticipated results of the DIAN-TU clinical trial of solanezumab and gantenerumab, and of robust phospho-tau plasma tests. The online stream also brought new data on a range of trials against tau, α-synuclein, and other targets in age-related neurodegenerative disease, and on pathogenesis and other topics.
At AAT-ADPD, researchers report how they built on prior reports that a person’s blood level of p-tau181 tells if they have Alzheimer’s.
P-tau217 appears sooner than p-tau181 in the brain, and it distinguishes AD from controls and other dementias even more cleanly.
Data shown at AAT-AD/PD explain why the DIAN-TU trial missed its primary endpoint. But gantenerumab strongly reduced plaques, tau, phospho-tau, and slowed NfL. This result prompted an open-label extension, sustaining hope for efficacy.
The AAT-AD/PD conference hosted a virtual conversation about what the trial’s disappointing cognitive and tantalizing biomarker data might mean. Hidden between thank you’s and pledges to stay committed were substantive points of debate and context.
In a Phase 2 trial, the vaccine reportedly normalized the rise in plasma NfL, and appeared to lower CSF tau and retard brain atrophy.
Researchers at the online AAT-AD/PD meeting touted therapies that target neuroinflammation, synapses, epigenetic regulation, or the cortisol stress response.
In people with Alzheimer’s biomarkers, the basal forebrain shrinks early, foreshadowing microglial neurotoxicity, atrophy in the medial temporal lobe, and cognitive decline.
Scientists report at AAT-AD/PD that they tightened a causal connection between gut microbes, microglial function, and protein deposits. In mice, that is.
For people with Parkinson’s, carrying Alzheimer’s genetic risk variants upped their odds of harboring Aβ and tau pathology and getting dementia. In people with DLB, Aβ plaques worsened tau and Lewy pathology, and cognition.
In a mouse model of amyloidosis, human wild-type TREM2 kept Aβ deposition at bay early on, but this defense became overwhelmed as plaques grew. The R47H AD risk variant never offered protection early on, and made things worse later.
Trialists are shooting new arrows at the disease, including compounds that tweak autophagy, neuroinflammation, and glycolipid recycling.
The first topline Phase 2 results from an antibody targeting Parkinson’s pathology, Roche’s prasinezumab, were a mixed bag. Next steps are unclear.