1.Psychological well-being trajectories preceding incident mild cognitive impairment and dementia

DOI: 10.1136/jnnp-2024-333837

https://jnnp.bmj.com/content/early/2024/07/13/jnnp-2024-333837

Dementia is a growing global concern, with increasing evidence suggesting a link between mental health and cognitive aging. However, the changes in mental health throughout the progression of dementia remain unclear. This study analyzes data from a 14-year longitudinal study of 910 cognitively intact older adults. Through a series of mental health assessments and the application of diagnostic criteria for Mild Cognitive Impairment (MCI), the study found that those who developed MCI experienced a more rapid decline in mental health. Additionally, regardless of whether MCI patients eventually progressed to dementia, their overall sense of well-being followed a similar trajectory.

For more detailed information, please refer to the original study.

2.Cortical neurodegeneration caused by Psen1 mutations is independent of Aβ

DOI: 10.1073/pnas.2409343121

https://www.pnas.org/doi/10.1073/pnas.2409343121

Over the past 20 years, amyloid-beta (Aβ) peptides have been a central focus in therapeutic approaches for Alzheimer's disease. Mutations in the PSEN gene are known to be a major cause of familial Alzheimer's disease, and presenilin (PS), as the catalytic subunit of γ-secretase, plays a key role in cleaving type I transmembrane proteins, including the amyloid precursor protein (APP), to release Aβ peptides. This article explores whether the complete removal of Aβ, due to defects in APP, can effectively prevent age-dependent neurodegeneration in Psen mutant mice. The study's findings indicate that the Psen1 mutation induces age-dependent neurodegeneration independent of Aβ, providing further support for the loss-of-function pathogenic mechanism underlying PSEN mutations.

For more detailed information, please refer to the original study.

3.Neuroimaging correlates of Alzheimer's disease biomarker concentrations in a racially diverse high-risk cohort of middle-aged adults

DOI: 10.1002/alz.14051

https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.14051

Race is a social construct, and different socio-cultural groups can lead to biological differences in health outcomes. Defining cross-ethnic and racial group thresholds and trajectories for Alzheimer's disease (AD) biomarkers is a crucial step in addressing health disparities in diagnosis, disease progression, clinical trial enrollment, and prescription practices. This study compares 29 middle-aged African Americans and 47 non-Hispanic whites with cognitive impairment. The results suggest that precuneus DMN connectivity and temporal WMH may be associated with midlife Alzheimer's disease risk pathology, particularly among African Americans.

For more detailed information, please refer to the original study.

4.PM2.5 triggers tau aggregation in a mouse model of tauopathy

DOI: 10.1172/jci.insight.176703

https://insight.jci.org/articles/view/176703

Tau protein aggregation is widely considered one of the hallmarks of Alzheimer's disease (AD). However, the molecular mechanisms underlying the assembly and spread of tau pathology remain unclear. Emerging research data suggest that exposure to fine particulate matter (PM2.5) is associated with an increased risk of AD. This article builds on this premise through related mouse trials, which demonstrate that PM2.5 exposure promotes tau pathology and induces cognitive impairment.

For more detailed information, please refer to the original study.

5.Spatial and temporal patterns of cortical mean diffusivity in Alzheimer's disease and suspected non-Alzheimer's disease pathophysiology

DOI: 10.1002/alz.14176

https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.14176

The accumulation of extracellular amyloid-beta (Aβ) plaques and intracellular neurofibrillary tau tangles (NFTs) are two core features of Alzheimer's disease (AD). Positron Emission Tomography (PET) imaging of Aβ and tau is commonly used as a surrogate for assessing Aβ plaques and tau tangles in AD. While most studies have used Diffusion-Weighted Imaging (DWI) to evaluate microstructural changes in white matter, there is growing evidence that cortical mean diffusivity (cMD) can also capture isotropic microstructural changes in gray matter in both AD and non-AD conditions. This study, based on diffusion and 3D T1-weighted Magnetic Resonance Imaging (MRI) images from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort, analyzes the baseline and longitudinal changes in cMD, cortical thickness (CTh), and gray matter volume (GMV). The goal is to investigate the cross-sectional and longitudinal characteristics of cMD, CTh, and GMV and their correlations with age.

For more detailed information, please refer to the original study.