07 Apr 2021
Part 2 of a two-part story. Click here for Part 1.
The COVID-19 pandemic has touched every aspect of health, from neurologic disease broadly (see Part 1 of this story) to clinical research. At the 15th International Conference on Alzheimer s and Parkinson s Diseases, held virtually March 9–14, clinical investigators talked about how they tried to prevail despite interruptions and preserve their trials. Looking to the future, how they will handle people who had COVID-19, or develop it during a trial, remains unclear.
Home nursing allowed dosing to continue in Roche s gantenerumab trials.
Other trials used telemedicine to continue recruitment and interventions.
How will researchers include people who had COVID in clinical trials?
07 Apr 2021
Part 1 of a two-part story. Click here for Part 2.
As COVID-19 drove yet another conference online, it was also the topic of discussions there held from the dull safety of researchers home screens. At the 15th International Conference on Alzheimer s and Parkinson s Diseases, held virtually March 9–14, clinicians grappled with neurological symptoms they see in people with the disease, and they discussed what COVID complications could mean for people with preclinical dementia. Researchers pointed to activated microglia as the culprit behind COVID delirium. Trial investigators also described how they minimized lockdown disruptions and debated how to include people who had COVID in future trials (see Part 10 of this conference series).
28 Feb 2021
Epidemiological evidence of herpes involvement in dementia continues to accrue. The latest finding comes from a Swedish cohort of 530,000 people, all over 50 years old. In the February 14 Alzheimer’s & Dementia, researchers led by Hugo Lövheim, Umeå University, reported that untreated herpes infection upped long-term dementia risk 1.5-fold, and antiviral treatment lowered risk by 11 percent. This is consistent with previous findings in Asian and European cohorts.
Whether herpes virus infection can contribute to AD has been hotly contested. Nationwide epidemiological studies have been gaining steam in the past few years, offering real-world evidence of a potential link. In Taiwan, people with severe herpes or shingles had a 2.5-3 times higher risk of dementia; antiviral treatment substantially reduced risk (Tsai et al., 2017; Chen et al., 2018; Tzeng et al., 2018). In South Korea, a shingles diagnosis came with a 12 percent higher risk of dementia; antivirals reduced
06 Feb 2021
A new APP knock-in mouse has hit the scene. Researchers led by Pascal Sanchez, Denali Therapeutics, San Francisco, California, described the details in a paper posted to bioRxiv on January 20. They humanized the Aβ sequence in the mouse APP gene and knocked in three familial Alzheimer’s disease mutations: Swedish, Arctic, and Austrian. TREM2 expression and cytokine concentrations spiked in brain tissue, microglia flocked to plaques, neurites swelled, and tau and neurofilament light collected in their cerebrospinal fluid. Notably, microglia surrounding plaques seemed distressed the cells filled with lipids and revved up transcription of genes previously linked to a subset of microglia isolated from AD brain tissue. Denali, in collaboration with the Jackson Laboratory, will make this model open access for academics and companies alike.
15 Dec 2020
Can making ephemeral anti-inflammatory fatty acids stick around a little longer protect people against Alzheimer’s disease? It just might, according to a study by Hui Zheng and colleagues at the Baylor College of Medicine, Houston, published December 9 in Science Translational Medicine.
In AD brain and 5xFAD mice, epoxide hydrolase is up and its anti-inflammatory products are down.
Astrocytes express this lipid metabolism enzyme.
In mice, inhibiting it restored epoxy fatty acids and a chain of consequences at molecular, synaptic, and behavioral levels of investigation.
These so-called epoxy fatty acids, or EpFAs, protect neurons; alas, epoxide hydrolases quickly break them down. The scientists found more epoxide hydrolase in brain tissue from people with AD and 5xFAD mice than in controls, corresponding to fewer epoxy fatty acids in the mice. Long-term treatment with an inhibitor curbed the hydrolase and boosted EpFA concentration in the mice’s brains. Inhibiting