Lancet Neurol Annual Review: 2021 Neurology Summary of Alzheimer's Disease

Substantial progress in Alzheimer's research in 2021
.

The journal The Lancet Neurology has conducted an annual inventory of Alzheimer's disease research and concluded that 2021 will mark a new era in Alzheimer's disease treatment
.

After considerable controversy, aducanumab became the first disease-modifying therapy targeting amyloid beta to receive accelerated approval from the U.
S.
Food and Drug Administration (FDA)
.

The debate over the approval of aducanumab has centered on disease-modifying treatments that clear amyloid beta without an apparent clinical response, setting a precedent for the approval of other disease-modifying treatments based on biomarker response
.

An important outcome of this approval is that it ignites momentum for guidelines to identify which patients may be the best candidates for disease-modifying treatments targeting amyloid beta, as well as best practices for safely treating and monitoring them
.

 Another advance came from a phase 2 trial of donanemab in early-stage symptomatic Alzheimer's disease
.

At 76 weeks, donanemab reduced brain amyloid beta and resulted in a better composite score of cognition and increased ability to perform activities of daily living compared with the placebo group
.

At week 76, the change from baseline in the composite Alzheimer's Disease Rating Scale score was -6.
86 in the donanemab group and -10.
06 in the placebo group (difference, 3.
20; 95% CI 0.
12-6.
27; p=0.
04)
.

 While therapeutics targeting amyloid beta have received much attention, important advances have also been made in targeting tau.

.

The ADAMANT Phase 2 study evaluated the safety, tolerability, immunogenicity, clinical efficacy and biomarker response of the active tau vaccine AADvac1 in patients with mild Alzheimer's disease dementia
.

The safety profile was excellent, with more than 98% of vaccinated cohorts eliciting antibody responses
.

Decreased phosphorylation levels of CSF tau protein at threonine 217 (p-tau217) were observed in the treatment group compared to the placebo group, which was modulated by baseline p-tau217 levels in patients with higher p-tau217 at baseline Better response
.

 In 2021, molecular imaging biomarkers will also contribute to the understanding of disease mechanisms associated with microglial activation and tau proliferation
.

Studies measuring microglial activation with [11C]PBR28 PET as well as tau and amyloid-β PET show that microglial activation and tau accumulation propagate in parallel spatially, following brain circuits and neurofibrillary tangles tau Protein pathology staging
.

Furthermore, the findings of all three ligands suggest that beta amyloid enhances the effect of microglial activation on tau proliferation
.

 Furthermore, another important finding is the role of genetic variants of APOE in tau pathology and neurodegeneration
.

Investigating neuronal APOE expression levels and selective neuronal vulnerability in Alzheimer's disease by depleting or overexpressing neuronal APOE and finding a link between APOE expression, neuronal MHC-I expression, tau protein pathology, and neurodegeneration There is a causal relationship
.

This suggests a mechanism by which neuronal APOE expression correlates with MHC-I expression, associated with tau pathology and selective neurodegeneration
.

Another study investigated the APOE3-Val236Glu (APOE3-Jacksonville) variant that is protective against Alzheimer's dementia
.

The APOE3-Jacksonville variant was found to reduce APOE aggregation and enhance lipidation, which has important implications in designing APOE-targeted therapies
.

 Finally, in areas such as dementia with Lewy bodies, frontotemporal dementia, and vascular cognitive impairment, multisite consortia around the world are building on the findings of the Alzheimer's Disease Neuroimaging Initiative
.

Biomarker studies of the prodromal and preclinical stages of these diseases and their overlap with Alzheimer's disease pathology are the focus and lay the groundwork for the potential development of individualized combination therapies to address each proteinopathy, including Alpha-synuclein and TDP-43 in addition to beta amyloid and tau, and cerebrovascular disease processes
.

 In conclusion, 2021 marks a new era in Alzheimer's disease treatment
.

Year-end inventory ☟☟☟ 2021 neurology image reading good article summary 2021 neurology unmissable guidelines and consensus 2021 neurology classic cases Top 12, help you develop clinical thinking Don't miss it! Inventory of FDA-approved drug treatments in neurology in 2021 (21)00412-9