Biomarkers.

Background: Alzheimer's disease (AD) is the most prevalent neurodegenerative disease, yet our comprehension predominantly relies on studies within the non-Hispanic White (NHW) population. To address this, Accelerating Medicines Partnership in AD (AMP-AD) aimed to promote inclusivity in multi-omics AD research, to unravel unique molecular signatures and pathways. The study aimed to provide comprehensive insights into the proteomic landscape of AD across diverse racial groups.

Biomarkers.

Background: Cerebrospinal fluid (CSF) is an important source of protein biomarkers for diagnosis, risk stratification, and predicting treatment response in Alzheimer's disease (AD). Proximity to brain parenchyma suggests that CSF proteomic alterations may mirror brain pathological changes. Understanding the evolution of CSF proteomic changes and their alignment with concurrent brain pathology necessitates matched CSF and brain analyses, which are possible using animal models of AD pathology.

Developing Topics.

Background: The sigma-2 receptor (S2R) modulator CT1812 is a first-in-class investigational therapeutic, currently in Phase 2 clinical trials for Alzheimer's disease (AD). Preclinical and clinical studies have shown that CT1812 displaces Aβ oligomers from synapses and clears them from the brain into the cerebrospinal fluid, restoring cognitive performance in a transgenic mouse model of AD. To investigate the mechanism of action of CT1812 and enable biomarker discovery, a phosphoproteomic analysis of CSF samples from SHINE-A was performed.

Developing Topics.

Background: SHINE (NCT03507790, COG0201) is a Phase 2 randomized, double-blind, placebo-controlled 6-month trial, conducted to study the effect of the sigma-2 receptor (S2R) modulator CT1812 in patients with Alzheimer's disease (AD). An unbiased assessment of CSF proteomes from the patients that completed the SHINE trial was performed to identify pharmacodynamic (PD) biomarkers of target/pathway engagement and disease modification for CT1812.

Method: Tandem-mass tag mass spectrometry (TMT-MS) CSF proteomics was performed on baseline and end of study samples from an analysis of SHINE Part A and B to test the effects of two doses (100 mg, 300 mg; given orally, once daily) of CT1812 compared to placebo in mild to moderate AD patients.

Sleep, Mood, and Economic Preferences.

This study used daily experimental data from smart bands worn by 142 respondents to investigate the relationship between the number of minutes slept and self-reported mood. The results showed that more minutes of sleep were associated with improved mood. Time preferences, altruism, and trust were also associated with mood.